Digital Commons Network^™

Combination Of Hsp90 Inhibitors And Hsp70 Inducers Prevent Hydrochloric Acid-Induced Pulmonary Fibrosis In Rabbits, Ruben M. L. Colunga Biancatelli, Pavel A. Solopov, Tierney Day, Dan E. Austin Jr., Len E. Murray, John D. Catravas

Bioelectrics Publications

Combined therapies with Heat Shock Protein 90 (HSP90) inhibitors and Heat Shock Protein 70 (HSP70) inducers are gaining significant interest in cancer and cardiovascular research. Here, we tested the hypothesis that HSP90 inhibitors and HSP70 inducers, together, can block the development of pulmonary fibrosis. We exposed New Zealand White Rabbits to hydrochloric acid (HCl, 0.1 N, 1.5 mL/kg), one of the top five chemicals most commonly involved in accidental exposures and inhalation injuries worldwide, and treated animals with either the orally available HSP90 inhibitor TAS-116 (1.7 mg/kg 5x/week) or TAS-116 combined with the HSP70 inducer, geranylgeranyl acetone (GGA, 50 mg/kg, …

Efficacy And Safety Of 4-Month Rifapentine-Based Tuberculosis Treatments In Persons With Diabetes., Ekaterina V. Kurbatova, William C. Whitworth, Lakshmi Praveena Peddareddy, Patrick P. J. Phillips, Nigel A. Scott, Kia E. Bryant, Rodney Dawson, Sandra Wagner Cardoso, Wadzanai Samaneka, Melissa Engle, Ziyaad Waja, Erin Sizemore, Wendy Carr, Kelly E. Dooley, Radojka Savic, Susan Swindells, Richard E. Chaisson, Susan E. Dorman, Payam Nahid, Nhung V. Nguyen, Aids Clinical Trials Group A5349, Tuberculosis Trials Consortium Study 31

Journal Articles: Infectious Diseases

A previous study demonstrated noninferior efficacy of 4-month rifapentine/moxifloxacin regimen for tuberculosis (TB) treatment compared with the standard regimen. We explored results among study participants with diabetes. Among 2,516 randomized participants, 181 (7.2%) had diabetes. Of 166 participants with diabetes in the microbiologically eligible analysis group, 26.3% (15/57) had unfavorable outcomes in the control regimen, 13.8% (8/58) in the rifapentine/moxifloxacin regimen, and 29.4% (15/51) in the rifapentine regimen. The difference in proportion of unfavorable outcomes between the control and rifapentine/moxifloxacin arms in the microbiologically eligible analysis group was -12.5% (95% CI -27.0% to 1.9%); the difference between the control and …

Serum Metabolome Profiling In Patients With Mild Cognitive Impairment Reveals Sex Differences In Lipid Metabolism, Rocio Diaz Escarcega, Vijay Kumar M J, Vasilia E Kyriakopoulos, Guadalupe J Ortiz, Aaron M Gusdon, Huihui Fan, Pedram Peesh, Maria P Blasco Conesa, Gabriela Delevati Colpo, Hilda W Ahnstedt, Lucy Couture, Stella H Kim, Miriam Hinojosa, Christine M Farrell, Sean P Marrelli, Akihiko Urayama, Bhanu P Ganesh, Paul E Schulz, Louise D Mccullough, Andrey S Tsvetkov

Faculty, Staff and Student Publications

Alzheimer's disease (AD) affects more women than men. Although women live longer than men, it is not longevity alone, but other factors, including metabolic changes, that contribute to the higher risk of AD in women. Metabolic pathways have been implicated in AD progression, but studies to date examined targeted pathways, leaving many metabolites unmeasured. Sex is often a neglected biological variable, and most metabolomic studies were not designed to investigate sex differences in metabolomic profiles. Here, we performed untargeted metabolomic profiling of sera from male and female patients with mild cognitive impairment (MCI), a common precursor to AD, and matched …

Sex Differences In Brain Iron Deposition And Microglial Ferritin In Alzheimer’S Disease, Syed Mushfiqur Rahman, Chunfeng Tan, Akiyoshi Kakita, Jose Felix Moruno-Manchon

Faculty, Staff and Student Publications

Objective

Iron is the most abundant metal in the human brain, and plays a crucial role in many biological processes. However, disruptions in brain iron metabolism can lead to iron buildup, which occurs with aging and is linked to several brain disorders, including Alzheimer's disease. Microglia, the brain's resident immune cells, have the highest capacity to store iron, which is stored intracellularly within ferritin complexes. Importantly, women are at a higher risk of developing Alzheimer's disease and experience faster disease progression compared to men.

Methods

We used postmortem brain samples from patients with Alzheimer's disease and small vessel disease patients …

Reliability Of Popliteal Artery Flow-Mediated Dilation In The Seated Position, Taskina Akhter, Patrick B. Wilson, J. David Branch, Leryn J. Reynolds

Exercise Science Faculty Publications

Flow-mediated dilation (FMD), a noninvasive measure of endothelial function, is commonly measured in the popliteal artery in the supine and upright body positions. However, reliability studies of the measurement in these positions are not well studied. This study aimed to examine the trial-retrial and visit-to-visit reliability of popliteal artery FMD in the seated position. Popliteal artery FMD was measured in 20 healthy adults across two visits in the seated and prone positions to assess visit-to-visit reliability. Two measurements were taken for each body position at each visit to assess trial-retrial reliability. %FMD was calculated as the percent change from baseline …

Identification Of Potential Prophylactic Medical Countermeasures Against Acute Radiation Syndrome (Ars), Kia T. Liermann-Wooldrik, Arpita Chatterjee, Elizabeth A. Kosmacek, Molly Myers, Oluwaseun Adebisi, Louise Monga-Wells, Liu Mei, Michelle P. Takacs, Patrick H. Dussault, Daniel R. Draney, Robert Powers, James W. Checco, Chittibabu Guda, Tomáš Helikar, David B. Berkowitz, Kenneth W. Bayles, Alan H. Epstein, Lynnette Cary, Daryl J. Murry, Rebecca E. Oberley-Deegan

Journal Articles: Pathology and Microbiology

Acute radiation syndrome (ARS) occurs when hematopoietic or gastrointestinal cells are damaged by radiation exposure causing DNA damage to the bone marrow and gastrointestinal epithelial stem cell populations. In these highly proliferative cell types, DNA damage inhibits stem cell repopulation. In humans and animals, this inability to regenerate stem cells is lethal. Within this manuscript, several compounds, Amifostine, Captopril, Ciprofloxacin, PrC-210, 5-AED (5-androstene-3β,17β-diol), and 5-AET (5-androstene-3β,7β,17B-triol), are assessed for their ability to protect against ARS in an in vitro and/or in vivo setting. ARS was accomplished by irradiating mouse bone marrow cells or rat intestinal epithelial (IEC-6) cells in vitro …

Treatment Sequence With Tebentafusp And Immune Checkpoint Inhibitors In Patients With Metastatic Uveal Melanoma And Metastatic Gna11/Gnaq Mutant Melanocytic Tumors, Florentia Dimitriou, Marlana Orloff, Erica Koch Hein, Phil Cheng, Isaac Hughes, Ester Simeone, Kamaneh Montazeri, Piyush Grover, Inderjit Mehmi, Camille Gerard, Caroline Gaudy-Marqueste, Jean-Jacques Grob, Olivier Michielin, Omid Hamid, Georgina Long, Ryan Sullivan, Ellen Kapiteijn, Douglas Johnson, Paolo Ascierto, Anthony Joshua, Richard Carvajal, Marcus Butler, Jessica Hassel, Reinhard Dummer

Kimmel Cancer Center Faculty Papers

BACKGROUND: Metastatic uveal melanoma (mUM) is rare. Immune checkpoint inhibitors (ICIs) have shown modest efficacy in mUM. Tebentafusp prolonged overall survival (OS) in a phase 3 study. We aimed to investigate the efficacy and safety of the sequence of tebentafusp and ICIs.

METHODS: Patients with HLA-A * 02:01 positive mUM, or metastatic GNA11/GNAQ mutant melanocytic tumors treated with tebentafusp followed by ICIs (group 1) or the inverse sequence (group 2) at any treatment line were retrospectively identified. The primary objective was OS rate at 2 years.

RESULTS: 131 patients were included; 51 in group 1 and 80 in group 2. …

Microglial Trem2 Promotes Phagocytic Clearance Of Damaged Neurons After Status Epilepticus, Dale B Bosco, Vaclav Kremen, Koichiro Haruwaka, Shunyi Zhao, Lingxiao Wang, Blake A Ebner, Jiaying Zheng, Manling Xie, Aastha Dheer, Jadyn F Perry, Abhijeet Barath, Aivi T Nguyen, Gregory A Worrell, Long-Jun Wu

The Brown Foundation: Institute of Molecular Medicine

In the central nervous system, triggering receptor expressed on myeloid cells 2 (TREM2) is exclusively expressed by microglia and is critical for microglial proliferation, migration, and phagocytosis. Microglial TREM2 plays an important role in neurodegenerative diseases, such as Alzheimer's disease and amyotrophic lateral sclerosis. However, little is known about how TREM2 affects microglial function within epileptogenesis. To investigate this, we utilized male TREM2 knockout (KO) mice within the intra-amygdala kainic acid seizure model. Electroencephalographic analysis, immunocytochemistry, and RNA sequencing revealed that TREM2 deficiency significantly promoted seizure-induced pathology. We found that TREM2 KO increased both the severity of acute status epilepticus …

“No One Told You Life Was Gonna Be This Way”: A Qualitative Exploration Of Friendship Expectations And Reality In University Life, Michael Priestley, Hannah Rachael Slack, Miss Madiha Islam, Delia Fuhrmann, Emily Long, Sarah Crook, Juliet Foster, Sophie Homer, Nicola Byrom

School of Psychology

Introduction: Young adulthood (ages 18–25) is a high-risk period for loneliness, particularly during educational transitions. Loneliness has negative consequences for mental health, physical health, and educational achievement. Psychologists conceptualize loneliness as emerging from a discrepancy between expected and experienced social connection, but this has been under-explored during young adulthood. Method: Drawing on thematic analysis of eight focus groups with 21 young adults in the UK, this paper explores the differences between retrospective expectations and experience of social connection during the transition into university and the implications for loneliness. Results: Whilst social expectations, experiences, and preferences vary considerably, young adults' perception …

A Reflection-Spectroscopy Measured Skin Carotenoid Score Strongly Correlates With Plasma Concentrations Of All Major Dietary Carotenoid Species Except For Lycopene, Qiang Wu, Cheryl Webb Cherry, Stephanie Jilcott Pitts, Melissa N Laska, Neal Craft, Nancy E Moran

Children’s Nutrition Research Center Staff Publications

Skin carotenoids can be measured non-invasively using spectroscopy methods to provide a biomarker of total dietary carotenoid and carotenoid-rich fruit and vegetable intake. However, the degree to which skin carotenoid biomarkers reflect intakes of specific carotenoids must be determined for specific devices. Previously, findings were mixed regarding the correlation between reflection spectroscopy (RS)-assessed skin carotenoids and individual plasma carotenoid concentrations. The current study expands on prior analyses to examine the cross-sectional associations between adult RS-assessed skin carotenoids and individual carotenoid species intakes and plasma concentrations, controlling for potential covariates. We hypothesized that RS-assessed skin carotenoid scores would strongly correlate with …

Fecal Glucocorticoid Metabolite And T3 Profiles Of Orphaned Elephants Differ From Non-Orphaned Elephants In Zambia, Daniella E Chusyd, Janine L Brown, Steve Paris, Nicole Boisseau, Webster Mwaanga, Moses Kasongo, Lisa Olivier, Stephanie L Dickinson, Bailey Ortyl, Tessa Steiniche, Steven N Austad, David B Allison, Michael D Wasserman

Children’s Nutrition Research Center Staff Publications

Background: Elephants provide valuable insight into how early-life adverse events (ELAEs) associate with animal health and welfare because they can live to advanced ages, display extensive cognitive and memory capabilities, and rely heavily on social bonds. Although it is known that African savanna elephants that experienced ELAEs, such as being orphaned due to human activities, have altered behavioral outcomes, little is known regarding the physiological consequences associated with those stressors.

Methods: We compared fecal glucocorticoid (fGCM) and thyroid (fT3) metabolites as well as body condition scores (BCS) in rescued and rehabilitated orphaned (early-dry season: n = 20; late-dry season: n …

Examining The Impact African American Male Teachers Have On The Math Scores Of Underserved Students, Demetrice Thomas

Graduate Thesis and Dissertation post-2024

This study contributed to a growing body of evidence emphasizing that teacher identity profoundly influences not only how students learn but also how they perceive themselves and their potential. As Gershenson (2022) noted, “Black teachers provide benefits to all students, fostering higher achievement and stronger aspirations,” highlighting the essential role of diverse educators in shaping student success. Consistent academic gains observed among students taught by African American male teachers reinforce the urgent need for educational systems to prioritize equity not only in student outcomes but also in diversifying the teaching workforce. Despite African American male teachers comprising less than 2% …

Cardiac Timing Effects On Response Speed Are Modulated By Blood Pressure But Not Heart Rate Variability In Healthy Young Adults, Xiao Yang, Catalina Roldan, Michael Gazzanigo, Yasmine Nabulsi, Fang Fang

Research and Infrastructure Service Enterprise (RISE) Faculty Publications

Cardiac timing effects reflect the dynamic interplay between interoceptive and exteroceptive processes. Human information processing tends to be facilitated during cardiac diastole and inhibited during systole, reflecting autonomic regulation and the neuromodulation by baroreceptor afferents. Thus, blood pressure (BP) and vagally-mediated heart rate variability (vmHRV) are potential modulators of those effects. Additionally, cognitive control appears to play a critical role in the processes. However, whether cardiac timing effects are influenced by those factors remains unclear. The present study aimed to clarify these relationships. Fifty-one healthy young adults completed three experimental sessions to assess BP, short-term HRV, and cardiac timing effects. …

Deep Brain Stimulation For Childhood Treatment-Resistant Obsessive-Compulsive Disorder: Mental Health Clinician Views On Candidacy Factors, Ilona Cenolli, Tiffany A Campbell, Natalie Dorfman, Meghan Hurley, Jared N Smith, Kristin Kostick-Quenet, Eric A Storch, Jennifer Blumenthal-Barby, Gabriel Lázaro-Muñoz

Center for Medical Ethics and Health Policy Staff Publications

Introduction: Deep brain stimulation (DBS) is approved under a humanitarian device exemption to manage treatment-resistant obsessive-compulsive disorder (TR-OCD) in adults. It is possible that DBS may be trialed or used clinically off-label in children and adolescents with TR-OCD in the future. DBS is already used to manage treatment-resistant childhood dystonia. Evidence suggests it is a safe and effective intervention for certain types of dystonia. Important questions remain unanswered about the use of DBS in children and adolescents with TR-OCD, including whether mental health clinicians would refer pediatric patients for DBS, and who would be a good candidate for DBS.

Objectives: …

Use Of Machine Learning Models To Predict Microaspiration Measured By Tracheal Pepsin A., Annette Bourgault, Ilana Logvinov, Chang Liu, Rui Xie, Jan Powers Phd, Rn, Ccrn, Mary Lou Sole

Nursing Publications, Posters, & Presentations

BACKGROUND: Enteral feeding intolerance, a common type of gastrointestinal dysfunction leading to underfeeding, is associated with increased mortality. Tracheal pepsin A, an indicator of microaspiration, was found in 39% of patients within 24 hours of enteral feeding. Tracheal pepsin A is a potential biomarker of enteral feeding intolerance.

OBJECTIVE: To identify predictors of microaspiration (tracheal or oral pepsin A). It was hypothesized that variables predicting the presence of tracheal pepsin A might be similar to predictors of enteral feeding intolerance.

METHODS: In this secondary analysis, machine learning models were fit for 283 adults receiving mechanical ventilation who had tracheal and …

A Serum Biomarker Panel And Miniarray Detection System For Tracking Disease Activity And Flare Risk In Lupus Nephritis, Chenling Tang, Gongjun Tan, Aygun Teymur, Jiechang Guo, Arturo Haces-Garcia, Weihang Zhu, Richard Williams, Jing Ning, Ramesh Saxena, Tianfu Wu

Faculty, Staff and Student Publications

Introduction: Lupus nephritis (LN) leads to end stage renal disease (ESRD), and early diagnosis and disease monitoring of LN could significantly reduce the risk. however, there is not such a system clinically. In this study we aim to develop a biomarker-panel based point-of-care system for LN.

Methods: Immunoassay screening combined with genomic expression databases and machine learning techniques was used to identify a biomarker panel of LN. A quantitative biomarker-panel mini-array (BPMA) system was developed and the sensitivity, specificity, reproducibility, and stability of the were examined. The performance of BPMA in disease monitoring was validated with machine models using a …

Magnetization Transfer Ratio In The Typically Developing Pediatric Spinal Cord: Normative Data And Age Correlation, Sara Naghizadeh Kashani, Iswarya Vel, Zahra Sadeghi Adl, Shiva Shahrampour, Devon Middleton, Mahdi Alizadeh, Laura Krisa, Scott Faro, Slimane Tounekti, Julien Cohen-Adad, Feroze Mohamed

Department of Radiology Faculty Papers

BACKGROUND AND PURPOSE: This study presents automated atlas-based magnetization transfer (MT) measurements of the typically developing pediatric cervical spinal cord (SC). We report normative MT ratio (MTR) values from the whole cervical cord white matter (WM) and WM tracts, examining variations with age, sex, height, and weight.

METHODS: MT scans of 33 healthy females (mean age = 12.8) and 22 males (mean age = 13.09) were acquired from the cervical SC (C2-C7) using a 3.0 T MRI. Data were processed using the SC Toolbox, segmented, and registered to the PAM50 template. Affine and non-rigid transformations co-registered the PAM50 WM atlas …

Type 2 Diabetes Polygenic Risk Score Interactions With Lifestyle Risk Factors In Black Americans, Ashley W Scadden, Aastha Kakar, Elizabeth M Litkowski, Mariah C Meyer, Nicole D Armstrong, Steven Buyske, Yanwei Cai, Iona Cheng, Burcu F Darst, Myriam Fornage, Mariaelisa Graff, Boya Guo, Christopher A Haiman, Heather M Highland, Charles Kooperberg, Loïc Le Marchand, Kari North, Ulrike Peters, Stephen S Rich, Jerome I Rotter, Vinodh Srinivasasainagendra, Hemant K Tiwari, Stephanie Waldrop, Kristin Young, Sridharan Raghavan, Ethan M Lange, Leslie A Lange, Marguerite R Irvin, Maggie A Stanislawski

The Brown Foundation: Institute of Molecular Medicine

Introduction: Prior work in predominantly European ancestry populations has explained how the risk associated with demographic, lifestyle, and health factors differs with underlying genetic susceptibility to type 2 diabetes (T2D), but less is known about these relationships in Black Americans.

Methods: We used covariate-adjusted logistic regression models of T2D to examine interactions between a published trans-ancestry derived T2D polygenic risk score (PRS) and various demographic, lifestyle, and health-related factors among 28,251 self-identified Black Americans from six cohort studies.

Results: The results are generally consistent with prior work in White populations. The PRS showed a significant interaction with body mass index, …

A Directed Content Analysis For Greatest Problems Among People With And Without Traumatic Brain Injury, Emily Dudek, Michael W Williams, Chung Lin Novelle Kew, Annalyn Demello, Brittany Wright, Alexandra B Holland, Alyssa Day-Gorman, Alexa S Gonzalez, Luis Leon Novelo, Xiangyi Liu, Shannon B Juengst

Faculty, Staff and Student Publications

Objective: To characterize the greatest problem or need among individuals with a history of traumatic brain injury (TBI), as compared with individuals with a history of other neurologic conditions, mental health conditions, and no history of neurologic or mental health conditions.

Design: A directed content analysis of open-text responses to a single online survey question using a framework guided by the Mayo-Portland Adaptability Inventory-4.

Setting: Community.

Participants: A total of 2861 community-dwelling adults (n=274 with TBI; n=289 with other neurologic conditions besides TBI; n=454 with mental health conditions but no neurologic conditions; and n=1844 controls).

Interventions: Not applicable.

Main outcome …

Psychometric Evaluation Of A Novel Measure Of Trauma-Related Cannabis Use To Cope, Sage E. Hawn, Terrell A. Hicks, Christopher Latourrette, Anita Thomas, Daniela Chaname, Sarah Ehlke, Abigail Powers Lott

Psychology Faculty Publications

Background: Posttraumatic stress disorder (PTSD) and cannabis use disorder (CUD) are commonly comorbid and are associated with many negative public health outcomes. One plausible explanation for this comorbidity comes from a self-medication framework, which suggests people use cannabis to cope with PTSD symptoms. Despite theoretical and empirical evidence for PTSD-related cannabis use to cope, no measure of this construct exists.

Objective: We sought to address this gap by developing and validating a novel measure of PTSD-specific cannabis self-medication, which we have termed the Trauma-Related Cannabis Use to Cope (TRCU) questionnaire.

Method: The psychometric properties of the TRCU and how it …

Vagally Mediated Heart Rate Variability Modulates The Association Between The Perceived Workload And The Stroop Effect On Behavioral Performance, Xiao Yang, Michael Gazzanigo, Fang Fang, Spencer House

Psychology Faculty Publications

Vagally mediated heart rate variability (vmHRV) reflects top-down cognitive processes involved in emotion-cognition integration. Using cognitive control can be effortful and increase negative affect. However, this intrinsic affective component of cognitive control has not been well studied, and the role of vmHRV in the association between subjective experience in using cognitive control and behavioral performance remains unknown. The current study aimed to examine the relationship of vmHRV with cognitive control and perceived workload in a cognitive task. Eighty-one participants performed the Stroop interference task. Participants rated subjective workload using the NASA Task Load Index (NASA-TLX) scale for congruent and incongruent …

Parent Ptsd, Social Support And Differential Associations With Facets Of Anxiety Sensitivity, Kristen Bermingham, Christopher Latourrette, Karen G. Chartier, Spit For Science Working Group, Ananda B. Amstadter, Kaitlin Bountress

Psychology Faculty Publications

Background: Anxiety Sensitivity (AS), the belief that anxiety experiences have negative implications, is a prospective predictor of posttraumatic stress disorder (PTSD) and has been linked to changes in PTSD in experimental studies. AS is comprised of three sub-components: cognitive, physical, and social concerns. PTSD is moderately heritable and parental PTSD may increase risk for these AS facets both directly and through environmental influences like reduced social support.

Objective: The present study will examine whether Parent PTSD is associated with reduced social support and in turn facets of AS.

Method: Participants were recruited from an ongoing longitudinal study of college student …

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 …

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 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 …

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 …

Safety Of Indocyanine Green Microdosing For Clinical Imaging Of Csf Ventricular Dynamics And Extracranial Outflow, Miriam Zamorano, Banghe Zhu, Ahmed T Massoud, Jonathan Hendricks, H Alex Choi, Pedram Peesh, Brandon A Miller, Xinhai Robert Zhang, Manish N Shah, Eva M Sevick-Muraca

Faculty, Staff and Student Publications

Background and purpose: Intravenous administration of indocyanine green (ICG) has been approved in brain surgeries for decades, yet concerns about neurotoxicity prevent its direct administration into the cerebrospinal fluid (CSF). Armed with prior animal studies demonstrating the feasibility of using ICG microdosing into the CSF, we sought to evaluate its nonclinical safety profile and obtain surrogate measures in adults prior to its use in human neonates.

Methods: Evaluation of ICG toxicity was conducted in mixed primary CNS cell cultures and in an extended safety study of juvenile rat pups deploying intraventricular injections of saline (as control) or ICG. Analysis of …

Peripheral Administration Of Blood From Tau Transgenic Animals Exacerbates Brain Tau-Associated Pathology, Laura Vegas-Gomez, Matias Pizarro, Jesus Garcia-Martin, Maria Angeles Arredondo-Alcala, Bianca Bustamante, Carolina Gonzalez-Silva, Soledad Matus, Rodrigo Diaz-Espinoza, Antonia Gutierrez, Rodrigo Morales, Claudia Duran-Aniotz, Ines Moreno-Gonzalez

Faculty, Staff and Student Publications

The accumulation of amyloid plaques and neurofibrillary tangles are pathological hallmarks of Alzheimer's disease (AD). While amyloid-beta propagation through prion-like mechanisms has been extensively studied in both central and peripheral pathways, the potential spreading of tau aggregates in the periphery remains largely unexplored. Emerging evidence suggests that hyperphosphorylated tau (ptau) aggregates may propagate beyond the central nervous system, as they have been detected in peripheral tissues and biological fluids from humans and mouse models of tauopathies. However, whether peripheral ptau aggregates or other factors associated to its accumulation contribute to brain pathology remains unclear. In this study, we investigate the …