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Behavioral Screening Reveals A Conserved Residue In Y-Box Rna-Binding Protein Required For Associative Learning And Memory In C Elegans, Ashley N Hayden, Katie L Brandel, Edward W Pietryk, Paul R Merlau, Priyadharshini Vijayakumar, Emily J Leptich, Elizabeth S Gaytan, Meredith I Williams, Connie W Ni, Hsiao-Tuan Chao, Jill A Rosenfeld, Rachel N Arey Oct 2024

Behavioral Screening Reveals A Conserved Residue In Y-Box Rna-Binding Protein Required For Associative Learning And Memory In C Elegans, Ashley N Hayden, Katie L Brandel, Edward W Pietryk, Paul R Merlau, Priyadharshini Vijayakumar, Emily J Leptich, Elizabeth S Gaytan, Meredith I Williams, Connie W Ni, Hsiao-Tuan Chao, Jill A Rosenfeld, Rachel N Arey

Faculty, Staff and Students Publications

RNA-binding proteins (RBPs) regulate translation and plasticity which are required for memory. RBP dysfunction has been linked to a range of neurological disorders where cognitive impairments are a key symptom. However, of the 2,000 RBPs in the human genome, many are uncharacterized with regards to neurological phenotypes. To address this, we used the model organism C. elegans to assess the role of 20 conserved RBPs in memory. We identified eight previously uncharacterized memory regulators, three of which are in the C. elegans Y-Box (CEY) RBP family. Of these, we determined that cey-1 is the closest ortholog to the mammalian Y-Box …


A Mouse Model For Conditional Expression Of Activated Β-Catenin In Epidermal Keratinocytes, Vineet K Maurya, Yan Ying, John P Lydon Oct 2024

A Mouse Model For Conditional Expression Of Activated Β-Catenin In Epidermal Keratinocytes, Vineet K Maurya, Yan Ying, John P Lydon

Faculty, Staff and Students Publications

We report the generation and characterization of the K5: CAT bigenic mouse in which the constitutively activated form of β-catenin (ΔN89 β-catenin) is conditionally expressed in cytokeratin-5 (K5) positive epidermal keratinocytes. Following short-term doxycycline intake during the telogen resting phase, the adult K5: CAT bigenic develops enlarged pilosebaceous units that expand deep into the dermis, an expansion usually observed during the anagen growth phase. Prolonged doxycycline treatment results in significant thickening and folding of the K5: CAT epidermis. During this persistent induction period, there is clear evidence of increased keratinocyte proliferation, particularly in the epidermal basal cell layer and the …


Rotavirus Vaccine Effectiveness Against Severe Acute Gastroenteritis: 2009-2022, Alpha Oumar Diallo, Mary E Wikswo, Iddrisu Sulemana, Leila C Sahni, Julie A Boom, Sasirekha Ramani, Rangaraj Selvarangan, Mary E Moffatt, Christopher J Harrison, Natasha Halasa, James Chappell, Laura Stewart, Mary Allen Staat, Elizabeth Schlaudecker, Christina Quigley, Eileen J Klein, Janet A Englund, Danielle M Zerr, Geoffrey A Weinberg, Peter G Szilagyi, Christina Albertin, Samantha H Johnston, John V Williams, Marian G Michaels, Robert W Hickey, Aaron T Curns, Michelle Honeywood, Slavica Mijatovic-Rustempasic, Mathew D Esona, Michael D Bowen, Umesh D Parashar, Rashi Gautam, Sara A Mirza, Jacqueline E Tate Oct 2024

Rotavirus Vaccine Effectiveness Against Severe Acute Gastroenteritis: 2009-2022, Alpha Oumar Diallo, Mary E Wikswo, Iddrisu Sulemana, Leila C Sahni, Julie A Boom, Sasirekha Ramani, Rangaraj Selvarangan, Mary E Moffatt, Christopher J Harrison, Natasha Halasa, James Chappell, Laura Stewart, Mary Allen Staat, Elizabeth Schlaudecker, Christina Quigley, Eileen J Klein, Janet A Englund, Danielle M Zerr, Geoffrey A Weinberg, Peter G Szilagyi, Christina Albertin, Samantha H Johnston, John V Williams, Marian G Michaels, Robert W Hickey, Aaron T Curns, Michelle Honeywood, Slavica Mijatovic-Rustempasic, Mathew D Esona, Michael D Bowen, Umesh D Parashar, Rashi Gautam, Sara A Mirza, Jacqueline E Tate

Faculty, Staff and Students Publications

Background: Rotavirus was the leading cause of acute gastroenteritis among US children until vaccine introduction in 2006, after which, substantial declines in severe rotavirus disease occurred. We evaluated rotavirus vaccine effectiveness (VE) over 13 years (2009-2022).

Methods: We analyzed data from the New Vaccine Surveillance Network using a test-negative case-control design to estimate rotavirus VE against laboratory-confirmed rotavirus infections among children seeking care for acute gastroenteritis (≥3 diarrhea or ≥1 vomiting episodes within 24 hours) in the emergency department (ED) or hospital. Case-patients and control-patients were children whose stool specimens tested rotavirus positive or negative, respectively, by enzyme immunoassay or …


Influenza C Virus In Us Children With Acute Respiratory Infection 2016–2019, Bethany K Sederdahl, Geoffrey A Weinberg, Angela P Campbell, Rangaraj Selvarangan, Jennifer E Schuster, Joana Y Lively, Samantha M Olson, Julie A Boom, Pedro A Piedra, Natasha B Halasa, Laura Stewart, Peter G Szilagyi, G K Balasubramani, Theresa Sax, Judith M Martin, Robert W Hickey, Marian G Michaels, John V Williams, New Vaccine Surveillance Network Oct 2024

Influenza C Virus In Us Children With Acute Respiratory Infection 2016–2019, Bethany K Sederdahl, Geoffrey A Weinberg, Angela P Campbell, Rangaraj Selvarangan, Jennifer E Schuster, Joana Y Lively, Samantha M Olson, Julie A Boom, Pedro A Piedra, Natasha B Halasa, Laura Stewart, Peter G Szilagyi, G K Balasubramani, Theresa Sax, Judith M Martin, Robert W Hickey, Marian G Michaels, John V Williams, New Vaccine Surveillance Network

Faculty, Staff and Students Publications

Influenza C virus (ICV) is an orthomyxovirus related to influenza A and B, yet due to few commercial assays, epidemiologic studies may underestimate incidence of ICV infection and disease. We describe the epidemiology and characteristics of ICV within the New Vaccine Surveillance Network (NVSN), a Centers for Disease Control and Prevention (CDC)-led network that conducts population-based surveillance for pediatric acute respiratory illness (ARI). Nasal or/combined throat swabs were collected from emergency department (ED) or inpatient ARI cases, or healthy controls, between 12/05/2016-10/31/2019 and tested by molecular assays for ICV and other respiratory viruses. Parent surveys and chart review were used …


Linkage Between Fuz And Gpr161 Genes Regulates Sonic Hedgehog Signaling During Mouse Neural Tube Development, Sung-Eun Kim, Hyun-Yi Kim, Bogdan J Wlodarczyk, Richard H Finnell Oct 2024

Linkage Between Fuz And Gpr161 Genes Regulates Sonic Hedgehog Signaling During Mouse Neural Tube Development, Sung-Eun Kim, Hyun-Yi Kim, Bogdan J Wlodarczyk, Richard H Finnell

Faculty, Staff and Students Publications

Sonic hedgehog (Shh) signaling regulates embryonic morphogenesis utilizing the primary cilium, the cell's antenna, which acts as a signaling hub. Fuz, an effector of planar cell polarity signaling, regulates Shh signaling by facilitating cilia formation, and the G protein-coupled receptor 161 (Gpr161) is a negative regulator of Shh signaling. The range of phenotypic malformations observed in mice bearing mutations in either of the genes encoding these proteins is similar; however, their functional relationship has not been previously explored. This study identified the genetic and biochemical linkage between Fuz and Gpr161 in mouse neural tube development. Fuz was found to be …


Perineuronal Nets’ Role In Metabolism, Nan Zhang, Beite Song, Peng Bai, Li Du, Lulu Chen, Yong Xu, Tianshu Zeng Oct 2024

Perineuronal Nets’ Role In Metabolism, Nan Zhang, Beite Song, Peng Bai, Li Du, Lulu Chen, Yong Xu, Tianshu Zeng

Faculty, Staff and Students Publications

Perineuronal nets (PNNs), specialized extracellular matrix (ECM) structures that envelop neurons, have recently been recognized as key players in the regulation of metabolism. This review explores the growing body of knowledge concerning PNNs and their role in metabolic control, drawing insights from recent research and relevant studies. The pivotal role of PNNs in the context of energy balance and whole body blood glucose is examined. This review also highlights novel findings, including the effects of astroglia, microglia, sex and gonadal hormones, nutritional regulation, circadian rhythms, and age on PNNs dynamics. These findings illuminate the complex and multifaceted role of PNNs …


Horizontal Gene Transfer And Beyond: The Delivery Of Biological Matter By Bacterial Membrane Vesicles To Host And Bacterial Cells, Alice X Wen, Christophe Herman Oct 2024

Horizontal Gene Transfer And Beyond: The Delivery Of Biological Matter By Bacterial Membrane Vesicles To Host And Bacterial Cells, Alice X Wen, Christophe Herman

Faculty, Staff and Students Publications

Membrane vesicles (MVs) are produced in all domains of life. In eukaryotes, extracellular vesicles have been shown to mediate the horizontal transfer of biological material between cells [1]. Therefore, bacterial MVs are also thought to mediate horizontal material transfer to host cells and other bacteria, especially in the context of cell stress. In this review, we discuss the mechanisms of bacterial MV production, evidence that their contents can be trafficked to host cells and other bacteria, and the biological relevance of horizontal material transfer by bacterial MVs.


Perspectives On Hand Hygiene In Belizean Healthcare Facilities During The Covid-19 Pandemic: A Qualitative Evaluation With Healthcare Workers, Kelsey Mcdavid, Christina Craig, Anh N Ly, Nicholas Bivens, Francis Morey, Russell Manzanero, Gerhaldine Morazan, Ella Hawes, Alexandra Medley, Kristy Murray, Matthew Lozier Oct 2024

Perspectives On Hand Hygiene In Belizean Healthcare Facilities During The Covid-19 Pandemic: A Qualitative Evaluation With Healthcare Workers, Kelsey Mcdavid, Christina Craig, Anh N Ly, Nicholas Bivens, Francis Morey, Russell Manzanero, Gerhaldine Morazan, Ella Hawes, Alexandra Medley, Kristy Murray, Matthew Lozier

Faculty, Staff and Students Publications

The World Health Organization recommends healthcare workers (HCWs) practice hand hygiene (HH) while providing care. Making alcohol-based hand rub (ABHR) available at points of care is recommended during times of high patient volume, such as the COVID-19 pandemic. In low- and middle-income countries, such as Belize, there may be limited access to HH materials within healthcare facilities (HCF). This paper examines the motivators and barriers to HH among HCWs in the 11 largest public healthcare facilities in Belize and HCWs' experiences with an intervention. In 2021, focus group discussions (FGDs) gathered HCWs' HH perceptions and preferences. An intervention was then …


Intimate Partner Violence-Related Brain Injury: Unmasking And Addressing The Gaps, Carrie Esopenko, Divya Jain, Shambhu Prasad Adhikari, Kristen Dams-O'Connor, Michael Ellis, Halina Lin Haag, Elizabeth S Hovenden, Finian Keleher, Inga K Koerte, Hannah M Lindsey, Amy D Marshall, Karen Mason, J Scott Mcnally, Deleene S Menefee, Tricia L Merkley, Emma N Read, Philine Rojcyk, Sandy R Shultz, Mujun Sun, Danielle Toccalino, Eve M Valera, Paul Van Donkelaar, Cheryl Wellington, Elisabeth A Wilde Oct 2024

Intimate Partner Violence-Related Brain Injury: Unmasking And Addressing The Gaps, Carrie Esopenko, Divya Jain, Shambhu Prasad Adhikari, Kristen Dams-O'Connor, Michael Ellis, Halina Lin Haag, Elizabeth S Hovenden, Finian Keleher, Inga K Koerte, Hannah M Lindsey, Amy D Marshall, Karen Mason, J Scott Mcnally, Deleene S Menefee, Tricia L Merkley, Emma N Read, Philine Rojcyk, Sandy R Shultz, Mujun Sun, Danielle Toccalino, Eve M Valera, Paul Van Donkelaar, Cheryl Wellington, Elisabeth A Wilde

Faculty, Staff and Students Publications

Intimate partner violence (IPV) is a significant, global public health concern. Women, individuals with historically underrepresented identities, and disabilities are at high risk for IPV and tend to experience severe injuries. There has been growing concern about the risk of exposure to IPV-related head trauma, resulting in IPV-related brain injury (IPV-BI), and its health consequences. Past work suggests that a significant proportion of women exposed to IPV experience IPV-BI, likely representing a distinct phenotype compared with BI of other etiologies. An IPV-BI often co-occurs with psychological trauma and mental health complaints, leading to unique issues related to identifying, prognosticating, and …


Diagnostic Overshadowing: A Delayed Diagnosis Of Autism Spectrum Disorder In A Deaf Child, Quynh-Chi Dang, Michael Hoffman, Rachel St. John Sep 2024

Diagnostic Overshadowing: A Delayed Diagnosis Of Autism Spectrum Disorder In A Deaf Child, Quynh-Chi Dang, Michael Hoffman, Rachel St. John

Journal of Early Hearing Detection and Intervention

Diagnostic overshadowing occurs when a patient with a pre-existing diagnosis presents with symptoms that are attributed to the diagnosis, but actually reflect a separate issue. This diagnostic overshadowing can lead to delays in diagnosis, as well as disparities in health care and outcomes. The following case will provide an example in which diagnostic overshadowing contributed to the delay of an autism diagnosis in a child who is deaf. With at least 40 to 50% of children who are deaf or hard of hearing having at least one co-existing medical/developmental condition, and the current prevalence of autism at 1 in 36 …


Malignant Pleural Mesothelioma: A Comprehensive Review., Molly Jain Md, Morgan Crites Np-C, Patricia Rich Md, Bharat Bajantri Md Sep 2024

Malignant Pleural Mesothelioma: A Comprehensive Review., Molly Jain Md, Morgan Crites Np-C, Patricia Rich Md, Bharat Bajantri Md

Internal Medicine Residency

Mesotheliomas are hyperplastic tumors that envelop the serosal membranes that safeguard the body's external surfaces. Although certain instances may exhibit indolent characteristics, a significant number of tumors demonstrate rapid progression and a poor prognosis. Mesotheliomas are typically categorized as benign or malignant, with malignant mesothelioma being more frequently linked to asbestos exposure. Malignant pleural mesothelioma (MPM) predominantly impacts males and often emerges in the late 50 s or beyond, characterized by a median age of early 70 s among patients exposed to asbestos lasting from 2 to 4 decades. Respiratory exposure to asbestos particles leads to the development of malignant …


Nongenetic And Genetic Factors Associated With White Matter Brain Aging: Exposome-Wide And Genome-Wide Association Study, Li Feng, Halley S Milleson, Zhenyao Ye, Travis Canida, Hongjie Ke, Menglu Liang, Si Gao, Shuo Chen, L Elliot Hong, Peter Kochunov, David K Y Lei, Tianzhou Ma Sep 2024

Nongenetic And Genetic Factors Associated With White Matter Brain Aging: Exposome-Wide And Genome-Wide Association Study, Li Feng, Halley S Milleson, Zhenyao Ye, Travis Canida, Hongjie Ke, Menglu Liang, Si Gao, Shuo Chen, L Elliot Hong, Peter Kochunov, David K Y Lei, Tianzhou Ma

Faculty, Staff and Student Publications

BACKGROUND/OBJECTIVES: Human brain aging is a complex process that affects various aspects of brain function and structure, increasing susceptibility to neurological and psychiatric disorders. A number of nongenetic (e.g., environmental and lifestyle) and genetic risk factors are found to contribute to the varying rates at which the brain ages among individuals.

METHODS: In this paper, we conducted both an exposome-wide association study (XWAS) and a genome-wide association study (GWAS) on white matter brain aging in the UK Biobank, revealing the multifactorial nature of brain aging. We applied a machine learning algorithm and leveraged fractional anisotropy tract measurements from diffusion tensor …


Downregulation Of Piezo2 In The Detrusor Of Men With Bladder Outlet Obstruction And Its Association With Urinary Retention And Decreased Bladder Compliance, Carlos Henrique Suzuki Bellucci, Thiago Souto Hemerly, Luisa Resende Tenório De Albuquerque, Ruan Pimenta, Vanessa Guimaraes Schreiter, Sabrina Thalita Dos Reis, Jose De Bessa Jr, Katia Ramos Moreira Leite, Alberto Antunes, Boopathi Ettickan, William C. Nahas, Cristiano Mendes Gomes Sep 2024

Downregulation Of Piezo2 In The Detrusor Of Men With Bladder Outlet Obstruction And Its Association With Urinary Retention And Decreased Bladder Compliance, Carlos Henrique Suzuki Bellucci, Thiago Souto Hemerly, Luisa Resende Tenório De Albuquerque, Ruan Pimenta, Vanessa Guimaraes Schreiter, Sabrina Thalita Dos Reis, Jose De Bessa Jr, Katia Ramos Moreira Leite, Alberto Antunes, Boopathi Ettickan, William C. Nahas, Cristiano Mendes Gomes

Center for Translational Medicine Faculty Papers

PURPOSE: Recent research has highlighted the mechanotransducer PIEZO2 as a crucial factor in lower urinary tract function, demonstrating associations with bladder compliance (BC), bladder wall thickening, and elevated bladder pressure. We explored the hypothesis that PIEZO2 expression may be associated with lower urinary tract dysfunction in men with bladder outlet obstruction (BOO) due to benign prostatic hyperplasia (BPH).

METHODS: The study included a consecutive series of patients undergoing open prostatectomy for BPH at our hospital between September 2014 and January 2016. All participants underwent comprehensive preoperative evaluations, including urodynamic assessments. During prostatectomy, a full-thickness fragment of the bladder wall was …


Single-Cell Transcriptomes And Chromatin Accessibility Of Endothelial Cells Unravel Transcription Factors Associated With Dysregulated Angiogenesis In Systemic Sclerosis, Mengqi Huang, Tracy Tabib, Dinesh Khanna, Shervin Assassi, Robyn Domsic, Robert Lafyatis Sep 2024

Single-Cell Transcriptomes And Chromatin Accessibility Of Endothelial Cells Unravel Transcription Factors Associated With Dysregulated Angiogenesis In Systemic Sclerosis, Mengqi Huang, Tracy Tabib, Dinesh Khanna, Shervin Assassi, Robyn Domsic, Robert Lafyatis

Faculty, Staff and Student Publications

Objectives: Vasculopathy emerges early in systemic sclerosis (SSc) and links to endothelial cell (EC) injury and angiogenesis. Understanding EC transcriptomes and epigenomes is crucial for unravelling the mechanisms involved.

Methods: Transcriptomes and chromatin accessibility were assessed by single-cell RNA sequencing and single-nucleus transposase-accessible chromatin sequencing. Immunofluorescent staining of skin and proteomics assay were employed to confirm the altered SSc EC phenotypes. Gain-of-function assay was used to evaluate the effects of ETS transcription factors on human dermal ECs (hDECs).

Results: Both control and SSc ECs shared transcriptomic signatures of vascular linages (arterial, capillary and venous ECs) and lymphatic ECs. Arterial ECs …


Impact Of Essential Genes On The Success Of Genome Editing Experiments Generating 3313 New Genetically Engineered Mouse Lines, Hillary Elrick, Kevin A Peterson, Brandon J Willis, Denise G Lanza, Elif F Acar, Edward J Ryder, Lydia Teboul, Petr Kasparek, Marie-Christine Birling, David J Adams, Allan Bradley, Robert E Braun, Steve D Brown, Adam Caulder, Gemma F Codner, Francesco J Demayo, Mary E Dickinson, Brendan Doe, Graham Duddy, Marina Gertsenstein, Leslie O Goodwin, Yann Hérault, Lauri G Lintott, K C Kent Lloyd, Isabel Lorenzo, Matthew Mackenzie, Ann-Marie Mallon, Colin Mckerlie, Helen Parkinson, Ramiro Ramirez-Solis, John R Seavitt, Radislav Sedlacek, William C Skarnes, Damien Smedley, Sara Wells, Jacqueline K White, Joshua A Wood, International Mouse Phenotyping Consortium, Stephen A Murray, Jason D Heaney, Lauryl M J Nutter Sep 2024

Impact Of Essential Genes On The Success Of Genome Editing Experiments Generating 3313 New Genetically Engineered Mouse Lines, Hillary Elrick, Kevin A Peterson, Brandon J Willis, Denise G Lanza, Elif F Acar, Edward J Ryder, Lydia Teboul, Petr Kasparek, Marie-Christine Birling, David J Adams, Allan Bradley, Robert E Braun, Steve D Brown, Adam Caulder, Gemma F Codner, Francesco J Demayo, Mary E Dickinson, Brendan Doe, Graham Duddy, Marina Gertsenstein, Leslie O Goodwin, Yann Hérault, Lauri G Lintott, K C Kent Lloyd, Isabel Lorenzo, Matthew Mackenzie, Ann-Marie Mallon, Colin Mckerlie, Helen Parkinson, Ramiro Ramirez-Solis, John R Seavitt, Radislav Sedlacek, William C Skarnes, Damien Smedley, Sara Wells, Jacqueline K White, Joshua A Wood, International Mouse Phenotyping Consortium, Stephen A Murray, Jason D Heaney, Lauryl M J Nutter

Faculty, Staff and Students Publications

The International Mouse Phenotyping Consortium (IMPC) systematically produces and phenotypes mouse lines with presumptive null mutations to provide insight into gene function. The IMPC now uses the programmable RNA-guided nuclease Cas9 for its increased capacity and flexibility to efficiently generate null alleles in the C57BL/6N strain. In addition to being a valuable novel and accessible research resource, the production of 3313 knockout mouse lines using comparable protocols provides a rich dataset to analyze experimental and biological variables affecting in vivo gene engineering with Cas9. Mouse line production has two critical steps - generation of founders with the desired allele and …


Opportunities For Helicobacter Pylori Eradication Beyond Conventional Antibiotics, Camilia Metadea Aji Savitri, Kartika Afrida Fauzia, Ricky Indra Alfaray, Hafeza Aftab, Ari Fahrial Syam, Masrul Lubis, Yoshio Yamaoka, Muhammad Miftahussurur Sep 2024

Opportunities For Helicobacter Pylori Eradication Beyond Conventional Antibiotics, Camilia Metadea Aji Savitri, Kartika Afrida Fauzia, Ricky Indra Alfaray, Hafeza Aftab, Ari Fahrial Syam, Masrul Lubis, Yoshio Yamaoka, Muhammad Miftahussurur

Faculty, Staff and Students Publications

Helicobacter pylori (H. pylori) is a bacterium known to be associated with a significant risk of gastric cancer in addition to chronic gastritis, peptic ulcer, and MALT lymphoma. Although only a small percentage of patients infected with H. pylori develop gastric cancer, Gastric cancer causes more than 750,000 deaths worldwide, with 90% of cases being caused by H. pylori. The eradication of this bacterium rests on multiple drug regimens as guided by various consensus. However, the efficacy of empirical therapy is decreasing due to antimicrobial resistance. In addition, biofilm formation complicates eradication. As the search for new antibiotics …


S6k1 Controls Dna Damage Signaling Modulated By The Mrn Complex To Induce Radioresistance In Lung Cancer, Ali Calderon-Aparicio, Jun He, Nicole L. Simone Sep 2024

S6k1 Controls Dna Damage Signaling Modulated By The Mrn Complex To Induce Radioresistance In Lung Cancer, Ali Calderon-Aparicio, Jun He, Nicole L. Simone

Department of Radiation Oncology Faculty Papers

Radiation is a mainstay of lung cancer treatment; however, resistance frequently develops. Identifying novel therapeutic targets to increase radiation sensitivity is crucial. S6K1 is a serine/threonine kinase known to regulate protein translation which is associated with radioresistance, but the mechanisms involved are unknown. We proposed to determine whether S6K1 promotes radioresistance by regulating DNA repair in lung cancer. Colony formation, protein expression and proliferation were assessed. S6K1 was modulated pharmacologically by either PF-4708671 or genetically by Crispr-Cas9. Higher radioresistance levels in lung cancer cells were associated with lower phosphoactivation of MRN complex members, a key activator of radiation-induced DNA repair …


Broad Applicability Of The Goldspire™ Platform For The Treatment Of Solid Tumors, Jenny Zilberberg, Christopher Uhl, Charles B Scott, David W. Andrews, Mark A Exley Sep 2024

Broad Applicability Of The Goldspire™ Platform For The Treatment Of Solid Tumors, Jenny Zilberberg, Christopher Uhl, Charles B Scott, David W. Andrews, Mark A Exley

Department of Neurosurgery Faculty Papers

Goldspire™ is a personalized immunotherapy platform that combines whole tumor-derived cells with antisense oligonucleotide (IMV-001) against Insulin-Like Growth Factor-1 Receptor (IGF-1R) in biodiffusion chambers (BDCs; 0.1 μm pore). BDCs are exposed to 5-6 Gy and implanted at abdominal sites for ∼48 h to deliver an antigenic payload and immunostimulatory factors to train the immune system. Lead product IGV-001 was evaluated in newly diagnosed glioblastoma (ndGBM) patients in Phase 1a and 1b trials (NCT02507583). A Phase 2b study (NCT04485949) recently completed enrollment. Preventative treatment with tumor-specific products manufactured with Goldspire limited tumor progression and extended overall survival in mice challenged with …


Molecular Targets For Breast Cancer Therapy, Hamidreza Montazeri Aliabadi Sep 2024

Molecular Targets For Breast Cancer Therapy, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

"Breast cancer is by far the most common cancer in women, and for a while, it surpassed lung cancer as the most diagnosed cancer, regardless of gender, in 2020 [1]. Chemotherapy and hormone therapy are still the first line of treatment, despite extensive research in molecularly targeted drugs. Therefore, triple negative breast cancer (TNBC) is still known as the most challenging type for treatment due to the limited identified targets. Inherent and acquired resistance are still major hurdles in breast cancer therapy, which further highlights the importance of identifying new molecular targets in this battle. The inherent resistance of unresponsive …


Genomic And Socioeconomic Determinants Of Racial Disparities In Breast Cancer Survival: Insights From The All Of Us Program, Nubaira Rizvi, Hui Lyu, Leah Vaidya, Xiao Cheng Wu, Lucio Miele, Qingzhao Yu Sep 2024

Genomic And Socioeconomic Determinants Of Racial Disparities In Breast Cancer Survival: Insights From The All Of Us Program, Nubaira Rizvi, Hui Lyu, Leah Vaidya, Xiao Cheng Wu, Lucio Miele, Qingzhao Yu

School of Public Health Faculty Publications

Background: Breast cancer outcomes are worse among Black women in the U.S. compared to White women. While extensive research has focused on risk factors contributing to breast cancer; the role of genomic elements in health disparities between these racial groups remains unclear. This study aims to identify genomic variants and socioeconomic status (SES) determinants influencing racial disparities in breast cancer survival through multiple mediation analyses. Methods: Our investigation is based on the NIH-supported All of Us (AoU) program and analyzes 7452 female participants with malignant tumors of breast, including 5073 with genomic data. A log-rank test reveals significant racial differences …


A Dosimetric Comparison Of Treatment Techniques For Stereotactic Body Radiotherapy For Pancreatic Patients, Kameron Lemley Sep 2024

A Dosimetric Comparison Of Treatment Techniques For Stereotactic Body Radiotherapy For Pancreatic Patients, Kameron Lemley

Masters Projects

Stereotactic body radiotherapy (SBRT) is utilized in radiation therapy to deliver ablative radiation doses to tumor volumes while achieving high conformity and minimal dose to surrounding critical structures. This treatment technique allows for faster dose fall-off which allows tighter treatment margins. SBRT for pancreatic cancer has been investigated for its efficacy and has proven to be an effective treatment choice for neoadjuvant radiation therapy. Since pancreatic cancer is extremely aggressive with a high mortality rate, it is important to have a treatment option that can reduce cost and increase convenience for the patient while simultaneously providing a conformal treatment plan. …


Neuronal Alpha-Synuclein Disease Integrated Staging System Performance In Ppmi, Pasadena, And Spark Baseline Cohorts, Tien Dam, Gennaro Pagano, Michael C Brumm, Caroline Gochanour, Kathleen L Poston, Daniel Weintraub, Lana M Chahine, Christopher Coffey, Caroline M Tanner, Catherine M Kopil, Yuge Xiao, Sohini Chowdhury, Luis Concha-Marambio, Peter Dibiaso, Tatiana Foroud, Mark Frasier, Danna Jennings, Karl Kieburtz, Kalpana Merchant, Brit Mollenhauer, Thomas J Montine, Kelly Nudelman, John Seibyl, Todd Sherer, Andrew Singleton, Diane Stephenson, Matthew Stern, Claudio Soto, Eduardo Tolosa, Andrew Siderowf, Billy Dunn, Tanya Simuni, Kenneth Marek, Parkinson’S Progression Markers Initiative Collaborators Sep 2024

Neuronal Alpha-Synuclein Disease Integrated Staging System Performance In Ppmi, Pasadena, And Spark Baseline Cohorts, Tien Dam, Gennaro Pagano, Michael C Brumm, Caroline Gochanour, Kathleen L Poston, Daniel Weintraub, Lana M Chahine, Christopher Coffey, Caroline M Tanner, Catherine M Kopil, Yuge Xiao, Sohini Chowdhury, Luis Concha-Marambio, Peter Dibiaso, Tatiana Foroud, Mark Frasier, Danna Jennings, Karl Kieburtz, Kalpana Merchant, Brit Mollenhauer, Thomas J Montine, Kelly Nudelman, John Seibyl, Todd Sherer, Andrew Singleton, Diane Stephenson, Matthew Stern, Claudio Soto, Eduardo Tolosa, Andrew Siderowf, Billy Dunn, Tanya Simuni, Kenneth Marek, Parkinson’S Progression Markers Initiative Collaborators

Faculty, Staff and Student Publications

The Neuronal alpha-Synuclein Disease (NSD) biological definition and Integrated Staging System (NSD-ISS) provide a research framework to identify individuals with Lewy body pathology and stage them based on underlying biology and increasing degree of functional impairment. Utilizing data from the PPMI, PASADENA, and SPARK studies, we developed and applied biologic and clinical data-informed definitions for the NSD-ISS across the disease continuum. Individuals enrolled as Parkinson's disease, Prodromal, or Healthy Controls were defined and staged based on biological, clinical, and functional anchors at baseline. Across the three studies 1741 participants had SAA data and of these 1030 (59%) were S+ consistent …


Spatial Organization Of Adenylyl Cyclase And Its Impact On Dopamine Signaling In Neurons, Léa Ripoll, Yong Li, Carmen W Dessauer, Mark Von Zastrow Sep 2024

Spatial Organization Of Adenylyl Cyclase And Its Impact On Dopamine Signaling In Neurons, Léa Ripoll, Yong Li, Carmen W Dessauer, Mark Von Zastrow

Faculty, Staff and Student Publications

The cAMP cascade is increasingly recognized to transduce physiological effects locally through spatially limited cAMP gradients. However, little is known about how adenylyl cyclase enzymes that initiate cAMP gradients are localized. Here we address this question in physiologically relevant striatal neurons and investigate how AC localization impacts downstream signaling function. We show that the major striatal AC isoforms are differentially sorted between ciliary and extraciliary domains of the plasma membrane, and that one isoform, AC9, is uniquely concentrated in endosomes. We identify key sorting determinants in the N-terminal cytoplasmic domain responsible for isoform-specific localization. We further show that AC9-containing endosomes …


The Association Of The Oral Microbiota With Cognitive Functioning In Adolescence, Oxana Y Naumova, Pavel V Dobrynin, Galina V Khafizova, Elena L Grigorenko Sep 2024

The Association Of The Oral Microbiota With Cognitive Functioning In Adolescence, Oxana Y Naumova, Pavel V Dobrynin, Galina V Khafizova, Elena L Grigorenko

Faculty, Staff and Students Publications

Background: A growing body of research supports the role of the microbial communities residing in the digestive system in the host's cognitive functioning. Most of these studies have been focused on the gut microbiome and its association with clinical phenotypes in middle-aged and older adults. There is an insufficiency of population-based research exploring the association of normative cognitive functioning with the microbiome particularly with the oral microbiota.

Methods: In this study, using metagenomics and metabolomics, we characterized the salivary microbiome diversity in a sample of 51 males of Hispanic and African American origin aged 12-18 years and explored …


Usf2 And Tfeb Compete In Regulating Lysosomal And Autophagy Genes, Jaebeom Kim, Young Suk Yu, Yehwa Choi, Do Hui Lee, Soobin Han, Junhee Kwon, Taichi Noda, Masahito Ikawa, Dongha Kim, Hyunkyung Kim, Andrea Ballabio, Keun Il Kim, Sung Hee Baek Sep 2024

Usf2 And Tfeb Compete In Regulating Lysosomal And Autophagy Genes, Jaebeom Kim, Young Suk Yu, Yehwa Choi, Do Hui Lee, Soobin Han, Junhee Kwon, Taichi Noda, Masahito Ikawa, Dongha Kim, Hyunkyung Kim, Andrea Ballabio, Keun Il Kim, Sung Hee Baek

Duncan NRI Faculty and Staff Publications

Autophagy, a highly conserved self-digestion process crucial for cellular homeostasis, is triggered by various environmental signals, including nutrient scarcity. The regulation of lysosomal and autophagy-related processes is pivotal to maintaining cellular homeostasis and basal metabolism. The consequences of disrupting or diminishing lysosomal and autophagy systems have been investigated; however, information on the implications of hyperactivating lysosomal and autophagy genes on homeostasis is limited. Here, we present a mechanism of transcriptional repression involving upstream stimulatory factor 2 (USF2), which inhibits lysosomal and autophagy genes under nutrient-rich conditions. We find that USF2, together with HDAC1, binds to the CLEAR motif within lysosomal …


Management Strategies Of Cesarean Section Ectopic Pregnancy: A Case Report, Hannah E. Daley, Ava R. Hansen, Priyanka Raju Md, Jonathan Buerger Md Sep 2024

Management Strategies Of Cesarean Section Ectopic Pregnancy: A Case Report, Hannah E. Daley, Ava R. Hansen, Priyanka Raju Md, Jonathan Buerger Md

Transformative Medicine

Introduction:

Cesarean scar ectopic pregnancy is a rare form of pregnancy with potential life-threatening complications such as severe hemorrhage, uterine rupture, and emergency hysterectomy Currently, there is no consensus regarding a standardized treatment algorithm for this specific variant of ectopic pregnancies.

Case Description:

This case describes a 28-year-old female with history of two prior cesarean sections who was diagnosed with cesarean section scar ectopic pregnancy. Initial management with intramuscular methotrexate was unsuccessful in the setting of inadequate decrease in β-hCG level. The patient ultimately underwent surgical management with dilation and suction evacuation under ultrasound guidance for removal of the ectopic …


Study Protocol For Writing To Heal: A Culturally Based Brief Expressive Writing Intervention For Chinese Immigrant Breast Cancer Survivors, Qian Lu, Di Lun, Lenna Dawkins-Moultin, Yisheng Li, Minxing Chen, Sharon Hermes Giordano, James W Pennebaker, Lucy Young, Carol Wang Sep 2024

Study Protocol For Writing To Heal: A Culturally Based Brief Expressive Writing Intervention For Chinese Immigrant Breast Cancer Survivors, Qian Lu, Di Lun, Lenna Dawkins-Moultin, Yisheng Li, Minxing Chen, Sharon Hermes Giordano, James W Pennebaker, Lucy Young, Carol Wang

Faculty, Staff and Student Publications

BACKGROUND: This study uses a randomized controlled trial (RCT) to test the health benefits of expressive writing that is culturally adapted for Chinese immigrant breast cancer survivors (BCSs) and to characterize how acculturation moderates the effects of expressive writing interventions.

METHODS: We will recruit Chinese immigrant BCSs (N = 240) diagnosed with stage 0-III breast cancer and within 5 years of completion of primary treatment. Recruitment will occur primarily through community-based organizations and cancer registries. Participants will be randomly assigned either to a control condition to write about neutral topics or to one of two intervention conditions, self-regulation or self-cultivation, …


Sequencing-Based Detection Of Avian Influenza A(H5n1) Virus In Wastewater In Ten Cities, Michael J Tisza, Blake M Hanson, Justin R Clark, Li Wang, Katelyn Payne, Matthew C Ross, Kristina D Mena, Anna Gitter, Sara J Javornik Cregeen, Juwan Cormier, Vasanthi Avadhanula, Austen Terwilliger, John Balliew, Fuqing Wu, Janelle Rios, Jennifer Deegan, Pedro A Piedra, Joseph F Petrosino, Eric Boerwinkle, Anthony W Maresso Sep 2024

Sequencing-Based Detection Of Avian Influenza A(H5n1) Virus In Wastewater In Ten Cities, Michael J Tisza, Blake M Hanson, Justin R Clark, Li Wang, Katelyn Payne, Matthew C Ross, Kristina D Mena, Anna Gitter, Sara J Javornik Cregeen, Juwan Cormier, Vasanthi Avadhanula, Austen Terwilliger, John Balliew, Fuqing Wu, Janelle Rios, Jennifer Deegan, Pedro A Piedra, Joseph F Petrosino, Eric Boerwinkle, Anthony W Maresso

Faculty, Staff and Students Publications

No abstract provided.


Molecular Testing Of Environmental Samples As A Potential Source To Estimate Parasite Infection, Rojelio Mejia, Barton Slatko, Cristina Almazan, Ruben Cimino, Alejandro Krolewiecki, Natalia Montellano Duran, Jacob Edwin Valera Aspetty, Paola Andrea Vargas, Chiara Cássia Oliveira Amorim, Stefan Michael Geiger, Ricardo Toshio Fujiwara, Juan David Ramirez, Luz Marina Llangarí-Arizo, Irene Guadalupe, Liliana E Villanueva-Lizama, Julio Vladimir Cruz-Chan, María Leticia Ojeda, Eva Mereles Aranda, Sandra Ocampos Benedetti, Maritza Dalí Camones Rivera, Eddyson Montalvo Sabino, Carlos Pineda, Eric J Wetzel, Philip J Cooper Sep 2024

Molecular Testing Of Environmental Samples As A Potential Source To Estimate Parasite Infection, Rojelio Mejia, Barton Slatko, Cristina Almazan, Ruben Cimino, Alejandro Krolewiecki, Natalia Montellano Duran, Jacob Edwin Valera Aspetty, Paola Andrea Vargas, Chiara Cássia Oliveira Amorim, Stefan Michael Geiger, Ricardo Toshio Fujiwara, Juan David Ramirez, Luz Marina Llangarí-Arizo, Irene Guadalupe, Liliana E Villanueva-Lizama, Julio Vladimir Cruz-Chan, María Leticia Ojeda, Eva Mereles Aranda, Sandra Ocampos Benedetti, Maritza Dalí Camones Rivera, Eddyson Montalvo Sabino, Carlos Pineda, Eric J Wetzel, Philip J Cooper

Faculty, Staff and Students Publications

We discuss the potential usefulness of molecular testing of soil, dust, and water samples to detect medically important parasites, and where such testing could be used to supplement stool sampling in humans. A wide variety of parasites including protozoa and helminths, many of which are zoonotic, have an important infection reservoir in the environment. In some cases, this environmental period is essential for further parasite development. We describe the progress in implementing methods for the molecular detection of these parasites in soil across eight collaborating centers in Latin America and represent a variety of potential applications in improving our understanding …


Untargeted Metabolomic Biomarker Discovery For The Detection Of Ectopic Pregnancy, Onur Turkoglu, Ayse Citil, Ceren Katar, Ismail Mert, Robert A Quinn, Ray O Bahado-Singh, Stewart F Graham Sep 2024

Untargeted Metabolomic Biomarker Discovery For The Detection Of Ectopic Pregnancy, Onur Turkoglu, Ayse Citil, Ceren Katar, Ismail Mert, Robert A Quinn, Ray O Bahado-Singh, Stewart F Graham

Faculty, Staff and Students Publications

Ectopic pregnancy (EP) is the leading cause of maternal morbidity and mortality in the first trimester. Using an untargeted metabolomic approach, we sought to identify putative plasma biomarkers using tandem liquid chromatography-mass spectrometry for the detection of tubal EP. This case-control study included the prospective recruitment of 50 tubal EP cases and 50 early intrauterine pregnancy controls. To avoid over-fitting, logistic regression models were developed in a randomly selected discovery group (30 cases vs. 30 controls) and validated in the test group (20 cases vs. 20 controls). In total, 585 mass spectral features were detected, of which 221 molecular features …