Digital Commons Network^™

Prodromal Glutamatergic Modulation With Riluzole Impacts Glucose Homeostasis And Spatial Cognition In Alzheimer's Disease Mice., Caleigh A Findley, Samuel A Mcfadden, Makayla F Cox, Lindsey N Sime, Mackenzie R Peck, Kathleen Quinn, Andrzej Bartke, Kevin N Hascup, Erin R Hascup

Articles

BACKGROUND: Prior research supports a strong link between Alzheimer's disease (AD) and metabolic dysfunction that involves a multi-directional interaction between glucose, glutamatergic homeostasis, and amyloid pathology. Elevated soluble amyloid-β (Aβ) is an early biomarker for AD-associated cognitive decline that contributes to concurrent glutamatergic and metabolic dyshomeostasis in humans and male transgenic AD mice. Yet, it remains unclear how primary time-sensitive targeting of hippocampal glutamatergic activity may impact glucose regulation in an amyloidogenic mouse model. Previous studies have illustrated increased glucose uptake and metabolism using a neuroprotective glutamate modulator (riluzole), supporting the link between glucose and glutamatergic homeostasis.

OBJECTIVE: We hypothesized …

Nasal Accumulation And Metabolism Of Δ9-Tetrahydrocannabinol Following Aerosol (‘Vaping’) Administration In An Adolescent Rat Model, Alexa Torrens, Christina M Ruiz, Maricela X Martinez, Alex Mabou Tagne, Pritam Roy, Dakota Grimes, Faizy Ahmed, Valeria Lallai, Victoria Inshishian, Malia Bautista, Yen-Chu Chen, Marilyn A. Huestis, Aditi Das, Christie D Fowler, Stephen V Mahler, Daniele Piomelli

Institute of Emerging Health Professions Faculty Papers

Passive aerosol exposure to Δ9-tetrahydrocannabinol (THC) in laboratory animals results in faster onset of action and less extensive liver metabolism compared to most other administration routes and might thus provide an ecologically relevant model of human cannabis inhalation. Previous studies have, however, overlooked the possibility that rodents, as obligate nose breathers, may accumulate aerosolized THC in the nasal cavity, from where the drug might directly diffuse to the brain. To test this, we administered THC (ten 5-s puffs of 100 mg/mL of THC) to adolescent (31-day-old) Sprague-Dawley rats of both sexes. We used liquid chromatography/tandem mass spectrometry to quantify the …

Lifetime Inclusive Fitness Effects Of Cooperative Polygamy In The Acorn Woodpecker, Walter D. Koenig, Sahas Barve, Joseph Haydock, Eric L. Walters

Biological Sciences Faculty Publications

Although over 50 y have passed since W. D. Hamilton articulated kin selection and inclusive fitness as evolutionary explanations for altruistic behavior, quantifying inclusive fitness continues to be challenging. Here, using 30 y of data and two alternative methods, we outline an approach to measure lifetime inclusive fitness effects of cooperative polygamy (mate-sharing or cobreeding) in the cooperatively breeding acorn woodpecker Melanerpes formicivorus. For both sexes, the number of offspring (observed direct fitness) declined while the number of young parented by related cobreeders (observed indirect fitness effect) increased with cobreeding coalition size. Combining these two factors, the observed inclusive …

Selinexor In Combination With Weekly Paclitaxel In Patients With Metastatic Solid Tumors: Results Of An Open Label, Single-Center, Multi-Arm Phase 1b Study With Expansion Phase In Ovarian Cancer, Shannon N Westin, Siqing Fu, Apostolia Tsimberidou, Sarina Piha-Paul, Fechukwu Akhmedzhanov, Bulent Yilmaz, Lacey Mcquinn, Amanda L Brink, Jing Gong, Cheuk Hong Leung, Heather Lin, David S Hong, Shubham Pant, Brett Carter, Amir Jazaeri, David Gershenson, Anil K Sood, Robert L Coleman, Jatin Shah, Funda Meric-Bernstam, Aung Naing

Faculty, Staff and Student Publications

OBJECTIVE: Selinexor is a first-in-class, oral selective inhibitor of nuclear export (SINE) compound which blocks Exportin-1 (XPO1). Our objective was to determine maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of selinexor and weekly paclitaxel.

METHODS: This was an open label, single-center, multi-arm phase 1b study utilizing a "3 + 3" design and a "basket-type" expansion in recurrent solid tumors. Selinexor (60 mg or 80 mg twice weekly orally) and weekly paclitaxel (80 mg IV 2 week on, 1 week off) were one of 13 parallel arms. Efficacy was evaluated using RECIST version 1.1.

RESULTS: All 35 patients …

Gankyrin-Mediated Interaction Between Cancer Cells And Tumor-Associated Macrophages Facilitates Prostate Cancer Progression And Androgen Deprivation Therapy Resistance, Guang Peng, Chao Wang, Hongru Wang, Min Qu, Keqin Dong, Yongwei Yu, Yuquan Jiang, Sishun Gan, Xu Gao

Faculty, Staff and Student Publications

Increasing evidence reveals that the interaction between tumor cells and tumor-associated macrophages (TAMs) facilitates the progression of prostate cancer, but the related mechanisms remained unclear. This study determined how gankyrin, a component of the 19S regulatory complex of the 26S proteasome, regulates the progression and androgen deprivation therapy (ADT) resistance of prostate cancer through tumor cell-TAM interactions.

Associations Of Snfl With Clinico-Radiological Measures In A Large Ms Population., Elias S Sotirchos, Kathryn C Fitzgerald, Carol M Singh, Matthew D Smith, Maria Reyes-Mantilla, Carrie M Hersh, Megan H Hyland, Ryan Canissario, Sarah B Simmons, Georgina Arrambide, Xavier Montalban, Manuel Comabella, Robert T Naismith, Min Qiao, Lauren B Krupp, Jacqueline A Nicholas, Katja Akgün, Tjalf Ziemssen, Richard Rudick, Elizabeth Fisher, Robert A Bermel, Ellen M Mowry, Peter A Calabresi

Neuroscience Articles

OBJECTIVE: Evaluation of serum neurofilament light chain (sNfL), measured using high-throughput assays on widely accessible platforms in large, real-world MS populations, is a critical step for sNfL to be utilized in clinical practice.

METHODS: Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) is a network of healthcare institutions in the United States and Europe collecting standardized clinical/imaging data and biospecimens during routine clinic visits. sNfL was measured in 6974 MS and 201 healthy control (HC) participants, using a high-throughput, scalable immunoassay.

RESULTS: Elevated sNfL levels for age (sNfL-E) were found in 1238 MS participants (17.8%). Factors associated with …

Expanding Medicaid To Reduce Human Immunodeficiency Virus Transmission In Houston, Texas: Insights From A Modeling Study, Francis Lee, Aditya S Khanna, Camden J Hallmark, Richa Lavingia, Marlene Mcneese, Jing Zhao, Melanie L Mcneese, Salma Khuwaja, Babak M Ardestani, Nicholson Collier, Jonathan Ozik, Anna L Hotton, Nina T Harawa, John A Schneider, Kayo Fujimoto

Faculty, Staff and Student Publications

CONTEXT: Medicaid expansion has been nationally shown to improve engagement in the human immunodeficiency virus (HIV) treatment and prevention continua, which are vital steps to stopping the HIV epidemic. New HIV infections in the United States are disproportionately concentrated among young Black men who have sex with men (YBMSM). Houston, TX, is the most populous city in the Southern United States with a racially/ethnically diverse population that is located in 1 of 11 US states that have not yet expanded Medicaid coverage as of 2021.

METHODS: An agent-based model that incorporated the sexual networks of YBMSM was used to simulate …

Health-Related Quality Of Life And Recovery Capital Among Recovery Residents Taking Medication For Opioid Use Disorder In Texas, Elizabeth O Obekpa, Sheryl A Mccurdy, Vanessa Schick, Christine M Markham, Kathryn R Gallardo, Johnny Michael Wilkerson

Faculty, Staff and Student Publications

BACKGROUND: Recovery from opioid use disorder (OUD) includes improvements in health-related quality of life (HRQOL) and is supported by recovery capital (RC). Little is known about RC and HRQOL among recovery residents taking medication for OUD. We described HRQOL and RC and identified predictors of HRQOL.

METHODS: Project HOMES is an ongoing longitudinal study implemented in 14 recovery homes in Texas. This is a cross-sectional analysis of data from 358 participants' on HRQOL (five EQ-5D-5L dimensions-mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and RC (Assessment of Recovery Capital scores) collected from April 2021 to June 2023. Statistical analyses were conducted …

Post-Acute Sequelae Of Covid-19 And Longitudinal Antibody Levels In A Community-Based Cohort, Noa Kopplin, Angie Garcia, Annika Reczek, Kate Wilkinson, Sruthi Yekkaluri, Caitlin C Murphy, Jasmin Tiro, Alagar R Muthukumar, Andrew Masica, Amit G Singal

Faculty, Staff and Student Publications

BACKGROUND: Coronavirus disease 2019 (COVID-19) infection invokes variable immune responses and poses a risk of post-acute sequelae SARS-CoV-2 infection (PASC) symptoms; however, most data on natural history are derived from patients with severe infection. Further data are needed among patients with mild infection, who comprise most cases.

METHODS: The Dallas Fort-Worth (DFW) COVID-19 Prevalence Study included 21,597 community-dwelling adults (ages 18-89) who underwent COVID-19 PCR and anti-nucleocapsid antibody testing between July 2020 and March 2021. We invited participants with positive COVID-19 results (cases) and a subset with negative results (controls), matched on age, sex, race/ethnicity, and ZIP code, to complete …

Survival Of Cancer Survivors With A New Pancreatic Cancer Diagnosis, Sandi L Pruitt, Anna Tavakkoli, Hong Zhu, Daniel F Heitjan, David E Gerber, Amit G Singal, Ethan A Halm, Muhammad Shaalan Beg, Bhumika Maddineni, Ankit J Kansagra, Caitlin C Murphy

Faculty, Staff and Student Publications

BACKGROUND: Persons newly diagnosed with pancreas cancer and who have survived a previous cancer are often excluded from clinical trials, despite limited evidence about their prognosis. We examined the association between previous cancer and overall survival.

METHODS: This US population-based cohort study included older adults (aged ≥66 years) diagnosed with pancreas cancer between 2005 and 2015 in the linked Surveillance, Epidemiology, and End Results-Medicare data. We used Cox proportional hazards models to estimate stage-specific effects of previous cancer on overall survival, adjusting for sociodemographic, treatment, and tumor characteristics.

RESULTS: Of 32,783 patients, 18.7% were previously diagnosed with another cancer. The …

Plasma Protein Biomarkers Of Healthy Dietary Patterns: Results From The Atherosclerosis Risk In Communities Study And The Framingham Heart Study, Shutong Du, Jingsha Chen, Hyunju Kim, Maura E Walker, Alice H Lichtenstein, Nilanjan Chatterjee, Peter Ganz, Bing Yu, Ramachandran S Vasan, Josef Coresh, Casey M Rebholz

Faculty, Staff and Student Publications

Background: Molecular mechanisms underlying the benefits of healthy dietary patterns are poorly understood. Identifying protein biomarkers of dietary patterns can contribute to characterizing biological pathways influenced by food intake.

Objectives: This study aimed to identify protein biomarkers associated with four indexes of healthy dietary patterns: Healthy Eating Index-2015 (HEI-2015); Alternative Healthy Eating Index-2010 (AHEI-2010); DASH diet; and alternate Mediterranean Diet (aMED).

Methods: Analyses were conducted on 10,490 Black and White men and women aged 49-73 y from the ARIC study at visit 3 (1993-1995). Dietary intake data were collected using a food frequency questionnaire, and plasma proteins were quantified using …

Factors Associated With Hiv Testing And Treatment Among Young Black Msm And Trans Women In Three Jail Systems, Nicholas Antos, Rey Flores, Nina Harawa, Natascha Del Vecchio, Rodal Issema, Kayo Fujimoto, Aditya S Khanna, Angela Di Paola, John A Schneider, Anna L Hotton

Faculty, Staff and Student Publications

Black men who have sex with men (BMSM) and transgender women (BTW) are disproportionately affected by incarceration and HIV. We assessed factors associated with HIV testing and viral suppression among 176 incarcerated BMSM and BTW in Chicago, IL; Los Angeles, CA; and Houston, TX. In multivariable logistic regression, having a sexual orientation of bisexual, heterosexual, or other vs. gay or same-gender loving was associated with higher odds of testing in custody (aOR 8.97; 95% CI 1.95 - 41.24). Binge drinking (aOR 0.19; 95% CI 0.04 - 0.92) and being unemployed prior to incarceration (aOR 0.03; 95% CI 0.00 - 0.23) …

Maternal Perceptions Of Vaccinating Boys Against Human Papillomavirus (Hpv) In Seoul, South Korea: A Descriptive Exploratory Qualitative Study, Jihye Choi, Christine Markham, Irene Tamí-Maury, Sooyoun Kim, Paula Cuccaro

Faculty, Staff and Student Publications

Human Papillomavirus (HPV) vaccination is of paramount importance to reduce HPV-associated cancers in both genders. In South Korea, the prophylactic vaccine is recognized as prevention of cervical cancer with little attention given to male HPV vaccination. The purpose of this study was to explore perceptions of male HPV vaccination and underlying factors for vaccine hesitancy among mothers of unvaccinated boys in Seoul, Korea using a qualitative method. We used a purposive sampling strategy to recruit mothers of unvaccinated middle school-aged boys living in one of the 25 districts in Seoul, supplemented by a snowball sampling approach. We conducted one-on-one telephone …

Adverse Maternal Environment Alters Oprl1 Variant Expression In Mouse Hippocampus., Xingrao Ke, Yingliu Huang, Qi Fu, Amber Majnik, Venkatesh Sampath, Robert H. Lane

Manuscripts, Articles, Book Chapters and Other Papers

An adverse maternal environment (AME) and Western diet (WD) in early life predispose offspring toward cognitive impairment in humans and mice. Cognitive impairment associates with hippocampal dysfunction. An important regulator of hippocampal function is the hippocampal Nociceptin/Orphanin FQ (N/OFQ) system. Previous studies find links between dysregulation of hippocampal N/OFQ receptor (NOP) expression and impaired cognitive function. NOP is encoded by the opioid receptor-like 1 (Oprl1) gene that contains multiple mRNA variants and isoforms. Regulation of Oprl1 expression includes histone modifications within the promoter. We tested the hypothesis that an AME and a postweaning WD increase the expression of hippocampal Oprl1 …

Examining Sociodemographic Correlates Of Opioid Use, Misuse, And Use Disorders In The All Of Us Research Program, Hsueh-Han Yeh, Cathryn Peltz-Rauchman, Christine C Johnson, Pamala A Pawloski, David Chesla, Stephen C Waring, Alan B Stevens, Mara Epstein, Christine Joseph, Lisa R Miller-Matero, Hongsheng Gui, Amy Tang, Eric Boerwinkle, Mine Cicek, Cheryl R Clark, Elizabeth Cohn, Kelly Gebo, Roxana Loperena, Kelsey Mayo, Stephen Mockrin, Lucila Ohno-Machado, Sheri Schully, Andrea H Ramirez, Jun Qian, Brian K Ahmedani

Faculty, Staff and Student Publications

Background: The All of Us Research Program enrolls diverse US participants which provide a unique opportunity to better understand the problem of opioid use. This study aims to estimate the prevalence of opioid use and its association with sociodemographic characteristics from survey data and electronic health record (EHR).

Methods: A total of 214,206 participants were included in this study who competed survey modules and shared EHR data. Adjusted logistic regressions were used to explore the associations between sociodemographic characteristics and opioid use.

Results: The lifetime prevalence of street opioids was 4%, and the nonmedical use of prescription opioids was 9%. …

A Decade Of Blood-Brain Barrier Permeability Assays: Revisiting Old Traumatic Brain Injury Rat Data For New Insights And Experimental Design, Chris T Bolden, Scott D Olson, Charles S Cox

Faculty, Staff and Student Publications

Increased microvascular permeability at the level of the blood-brain barrier (BBB) often leads to vasogenic brain edema following traumatic brain injury (TBI). These pathologic conditions compromise the integrity of the neurovascular unit resulting in severe brain dysfunction. To quantify this permeability and assess ionic equillibrium, preclinical researchers have relied on the use of various molecular weight permeable dyes such as Evans Blue that normally cannot enter the brain parenchyma under homeostatic conditions. Evans Blue, the most cited of the molecular weight dyes, has reported reproducibility issues because of harsh extraction processes, suboptimal detection via absorbance, and wide excitation fluorescence spectra …

Association Between Brain Similarity To Severe Mental Illnesses And Comorbid Cerebral, Physical, And Cognitive Impairments, Yizhou Ma, Mark D Kvarta, Bhim M Adhikari, Joshua Chiappelli, Xiaoming Du, Andrew Van Der Vaart, Eric L Goldwaser, Heather Bruce, Kathryn S Hatch, Si Gao, Ann Summerfelt, Neda Jahanshad, Paul M Thompson, Thomas E Nichols, L Elliot Hong, Peter Kochunov

Faculty, Staff and Student Publications

Severe mental illnesses (SMIs) are often associated with compromised brain health, physical comorbidities, and cognitive deficits, but it is incompletely understood whether these comorbidities are intrinsic to SMI pathophysiology or secondary to having SMIs. We tested the hypothesis that cerebral, cardiometabolic, and cognitive impairments commonly observed in SMIs can be observed in non-psychiatric individuals with SMI-like brain patterns of deviation as seen on magnetic resonance imaging. 22,883 participants free of common neuropsychiatric conditions from the UK Biobank (age = 63.4 ± 7.5 years, range = 45–82 years, 50.9% female) were split into discovery and replication samples. The regional vulnerability index …

Population-Based Mini-Mental State Examination Norms In Adults Of Mexican Heritage In The Cameron County Hispanic Cohort, Avram S Bukhbinder, Miriam Hinojosa, Kristofer Harris, Xiaojin Li, Christine M Farrell, Madison Shyer, Nathan Goodwin, Sahar Anjum, Omar Hasan, Susan Cooper, Lois Sciba, Amanda Falk Vargas, David H Hunter, Guadalupe J Ortiz, Karen Chung, Licong Cui, Guo-Qiang Zhang, Susan P Fisher-Hoch, Joseph B Mccormick, Paul E Schulz

Faculty, Staff and Student Publications

Background:

Accurately identifying cognitive changes in Mexican American (MA) adults using the Mini-Mental State Examination (MMSE) requires knowledge of population-based norms for the MMSE, a scale which has widespread use in research settings.

Objective:

To describe the distribution of MMSE scores in a large cohort of MA adults, assess the impact of MMSE requirements on their clinical trial eligibility, and explore which factors are most strongly associated with their MMSE scores.

Methods:

Visits between 2004–2021 in the Cameron County Hispanic Cohort were analyzed. Eligible participants were ≥18 years old and of Mexican descent. MMSE distributions before and after stratification by …

Sex-Biased Autophagy As A Potential Mechanism Mediating Sex Differences In Ischemic Stroke Outcome, Brian Noh, Louise D Mccullough, Jose F Moruno-Manchon

Faculty, Staff and Student Publications

Stroke is the second leading cause of death and a major cause of disability worldwide, and biological sex is an important determining factor in stroke incidence and pathology. From childhood through adulthood, men have a higher incidence of stroke compared with women. Abundant research has confirmed the beneficial effects of estrogen in experimental ischemic stroke but genetic factors such as the X-chromosome complement can also play an important role in determining sex differences in stroke. Autophagy is a self-degrading cellular process orchestrated by multiple core proteins, which leads to the engulfment of cytoplasmic material and degradation of cargo after autophagy …

Family-Level Antecedents Of Children's Patterns Of Reactivity To Interparental Conflict: Testing The Reformulation Of Emotional Security Theory, Patrick T Davies, Joanna K Pearson, Vanessa T Cao, Melissa L Sturge-Apple

Faculty, Staff and Student Publications

Guided by emotional security theory, this study examined the family-level antecedents of children's reaction patterns to interparental conflict in a sample of 243 preschool children (M age = 4.60 years; 48% Black; 16% Latinx; 56% girls) and their parents in the Northeastern United States. Behavioral observations of children's responses to interparental conflict over two annual measurement occasions assessed their tendencies to exhibit four patterns of defending against threat: secure (i.e., efficiently address direct threats), mobilizing (i.e., high reactivity to potential threat and social opportunities), dominant (i.e., directly defeat threat), and demobilizing (i.e., reduce salience as a target of hostility). …

Risk Of Depression In A Suburban Primary Care Setting Before And During The Covid-19 Pandemic, Carman H Whiting, Pouran Yousefi, Jude K A Des Bordes, Nahid J Rianon

Faculty, Staff and Student Publications

INTRODUCTION: Major depression is a common disorder affecting millions of adults each year. Many population-based surveys showed an increase in the number people with symptoms of depression at the onset of the COVID-19 pandemic. Our aim was to determine and compare the prevalence of depression risk in a primary care setting before and during the COVID-19 pandemic.

METHODS: We conducted a cross-sectional study based on retrospective review of medical records from a large suburban primary care clinic. Records of adults 18 years and older, seen between January 1, 2019 and December 31, 2020 and who had also been screened for …

Timing Of Invasive Mechanical Ventilation And Death In Critically Ill Adults With Covid-19: A Multicenter Cohort Study, Adam Green, Jean-Sebastien Rachoin, Christa Schorr, Phil Dellinger, Jonathan D Casey, Isabel Park, Shruti Gupta, Rebecca M Baron, Shahzad Shaefi, Krystal Hunter, David E Leaf

Faculty, Staff and Student Publications

PURPOSE: To investigate if the timing of initiation of invasive mechanical ventilation (IMV) for critically ill patients with COVID-19 is associated with mortality.

MATERIALS AND METHODS: The data for this study were derived from a multicenter cohort study of critically ill adults with COVID-19 admitted to ICUs at 68 hospitals across the US from March 1 to July 1, 2020. We examined the association between early (ICU days 1-2) versus late (ICU days 3-7) initiation of IMV and time-to-death. Patients were followed until the first of hospital discharge, death, or 90 days. We adjusted for confounding using a multivariable Cox …

Radiotherapy Reimagined: Integrating Nanomedicines Into Radiotherapy Clinical Trials, Allison N Duross, Jack Phan, Alexander J Lazar, Joshua M Walker, Alexander R Guimaraes, Carole Baas, Sunil Krishnan, Charles R Thomas, Conroy Sun, Alexander F Bagley

Faculty, Staff and Student Publications

Radioenhancing nanoparticles (NPs) are being evaluated in ongoing clinical trials for various cancers including head and neck, lung, esophagus, pancreas, prostate, and soft tissue sarcoma. Supported by decades of preclinical investigation and recent randomized trial data establishing clinical activity, these agents are poised to influence future multimodality treatment paradigms involving radiotherapy. Although the physical interactions between NPs and ionizing radiation are well characterized, less is known about how these agents modify the tumor microenvironment, particularly regarding tumor immunogenicity. In this review, we describe the key multidisciplinary considerations related to radiation, surgery, immunology, and pathology for designing radioenhancing NP clinical trials. …

Associative Learning Contributes To The Persistence Of Fatigue-Like Behavior In Male Mice In A Model Of Cancer Survivorship, Elisabeth G Vichaya, Josephine K Darpolor, Phillip S Gross, Jessica M Molkentine, Daniel W Vermeer, Paola D Vermeer, John H Lee, Cullen M Taniguchi, Robert Dantzer

Faculty, Staff and Student Publications

Persistent fatigue is a debilitating side effect that impacts a significant proportion of cancer survivors for which there is not yet an FDA-approved treatment. While certainly a multi-factorial problem, persistent fatigue could be due, in part, to associations learned during treatment. Therefore, we sought to investigate the role of associative learning in the persistence of fatigue using a preclinical model of cancer survivorship. For this purpose, we used a murine model of human papilloma virus-related head and neck cancer paired with a curative regimen of cisplatin-based chemoradiation in male C57BL/6J mice. Fatigue-like behavior was assessed by measuring variations in voluntary …

Chronic Restraint Stress Impairs Voluntary Wheel Running But Has No Effect On Food-Motivated Behavior In Mice, Kiersten Scott, Thien Trong Phan, Nabila Boukelmoune, Cobi J Heijnen, Robert Dantzer

Faculty, Staff and Student Publications

Chronic restraint stress is known to cause significant alterations of mitochondrial biology. However, its effects on effort-based behavior and the sensitivity of these effects to treatments that restore mitochondrial function have not been assessed. Based on the hypothesis that the behavioral consequences of this stressor should be more severe for an energy demanding activity than for an energy procuring activity, we compared the effects of chronic restraint stress on the performance of male mice trained to use a running wheel or to nose poke for a food reward in an operant conditioning cage. In accordance with our hypothesis, we observed …

Targeted Genomic Sequencing Of Tsc1 And Tsc2 Reveals Causal Variants In Individuals For Whom Previous Genetic Testing For Tuberous Sclerosis Complex Was Normal, Hannah D West, Mark Nellist, Rutger W W Brouwer, Mirjam C G N Van Den Hout-Van Vroonhoven, Luiz Gustavo Dufner De Almeida, Femke Hendriks, Peter Elfferich, Meera Raja, Peter Giles, Rosa M Alfano, Angela Peron, Yves Sznajer, Liesbeth De Waele, Anna Jansen, Marije Koopmans, Anneke Kievit, Laura S Farach, Hope Northrup, Julian R Sampson, Laura E Thomas, Wilfred F J Van Ijcken

Faculty, Staff and Student Publications

Tuberous sclerosis complex (TSC) is caused by inactivating variants in TSC1 and TSC2. Somatic mosaicism, as well as the size and complexity of the TSC1 and TSC2 loci, makes variant identification challenging. Indeed, in some individuals with a clinical diagnosis of TSC, diagnostic testing fails to identify an inactivating variant. To improve TSC1 and TSC2 variant detection, we screened the TSC1 and TSC2 genomic regions using targeted HaloPlex custom capture and next-generation sequencing (NGS) in genomic DNA isolated from peripheral blood of individuals with definite, possible or suspected TSC in whom no disease-associated variant had been identified by previous …

Il-8 Produced Via Bidirectional Communication Between Prostate Cancer And M2 Macrophages As A Potential Diagnostic And Prognostic Biomarker, Huihui Fan, Zheng Tang, Yaling Tian, Qingsong Lv, Fangyin Zeng

Faculty, Staff and Student Publications

PURPOSE: Owing to the mortality associated with metastatic prostate cancer and the shortcomings of the current parameters in predicting the disease prognosis, we require the identification of viable biomarkers, which would help in the diagnosis and prognosis of the disease. We aimed to determine whether the interleukin-8 level in the tumor microenvironment could serve as a potential clinical diagnostic marker and prognostic factor for prostate cancer.

METHODS: The migration assay of prostate cancer cells was performed in an in vitro co-culture model. Cell lines PC3 and DU145 were divided into two groups and co-cultured with M0 and M2 macrophages, respectively. …

Autologous T Cell Therapy For Mage-A4+ Solid Cancers In Hla-A*02+ Patients: A Phase 1 Trial, David S Hong, Brian A Van Tine, Swethajit Biswas, Cheryl Mcalpine, Melissa L Johnson, Anthony J Olszanski, Jeffrey M Clarke, Dejka Araujo, George R Blumenschein, Partow Kebriaei, Quan Lin, Alex J Tipping, Joseph P Sanderson, Ruoxi Wang, Trupti Trivedi, Thejo Annareddy, Jane Bai, Stavros Rafail, Amy Sun, Lilliam Fernandes, Jean-Marc Navenot, Frederic D Bushman, John K Everett, Derin Karadeniz, Robyn Broad, Martin Isabelle, Revashnee Naidoo, Natalie Bath, Gareth Betts, Zohar Wolchinsky, Dzmitry G Batrakou, Erin Van Winkle, Erica Elefant, Armin Ghobadi, Amanda Cashen, Anne Grand'maison, Philip Mccarthy, Paula M Fracasso, Elliot Norry, Dennis Williams, Mihaela Druta, David A Liebner, Kunle Odunsi, Marcus O Butler

Faculty, Staff and Student Publications

Affinity-optimized T cell receptors can enhance the potency of adoptive T cell therapy. Afamitresgene autoleucel (afami-cel) is a human leukocyte antigen-restricted autologous T cell therapy targeting melanoma-associated antigen A4 (MAGE-A4), a cancer/testis antigen expressed at varying levels in multiple solid tumors. We conducted a multicenter, dose-escalation, phase 1 trial in patients with relapsed/refractory metastatic solid tumors expressing MAGE-A4, including synovial sarcoma (SS), ovarian cancer and head and neck cancer ( NCT03132922 ). The primary endpoint was safety, and the secondary efficacy endpoints included overall response rate (ORR) and duration of response. All patients (N = 38, nine tumor types) experienced …

Hras Mutations Define A Distinct Subgroup In Head And Neck Squamous Cell Carcinoma, Niamh Coleman, Kathrina L Marcelo, Julia F Hopkins, Nusrat Israr Khan, Robyn Du, Lingzhi Hong, Edward Park, Binaifer Balsara, Mollie Leoni, Curtis Pickering, Jeffrey Myers, John Heymach, Lee A Albacker, David Hong, Maura Gillison, Xiuning Le

Faculty, Staff and Student Publications

Purpose: In head and neck squamous cell carcinoma (HNSCC), HRAS mutation is a new actionable oncogene driver. We aimed to evaluate HRAS mutational variants, comutation profile, and survival outcomes of this molecularly defined population.

Methods: We leveraged four deidentified patient data sets with HRAS-mutant HNSCC, MD Anderson Cancer Center, Kura Oncology, Inc trial, Foundation Medicine, and American Association for Cancer Research GENIE v.12. Patient demographic information and clinical courses were extracted, when available, in addition to HRAS mutation type and co-occurring mutations. Survival outcomes were analyzed (Kaplan-Meier method).

Results: Two hundred forty-nine patients with HRAS-mutant HNSCC were identified …

Biological Embedding Of Early Trauma: The Role Of Higher Prefrontal Synaptic Strength, Amanda J F Tamman, Lihong Jiang, Christopher L Averill, Graeme F Mason, Lynnette A Averill, Chadi G Abdallah

Staff and Researcher Publications

Background: Early trauma predicts poor psychological and physical health. Glutamatergic synaptic processes offer one avenue for understanding this relationship, given glutamate's abundance and involvement in reward and stress sensitivity, emotion, and learning. Trauma-induced glutamatergic excitotoxicity may alter neuroplasticity and approach/avoidance tendencies, increasing risk for psychiatric disorders. Studies examine upstream or downstream effects instead of glutamatergic synaptic processes in vivo, limiting understanding of how trauma affects the brain.Objective: In a pilot study using a previously published data set, we examine associations between early trauma and a proposed measure of synaptic strength in vivo in one of the largest human …