Digital Commons Network^™

Icos And Icos Ligand: Expression Patterns And Outcomes In Oncology Patients, Mina Nikanjam, Shumei Kato, Daisuke Nishizaki, Donald A Barkauskas, Sarabjot Pabla, Mary K Nesline, Jeffrey M Conroy, Aung Naing, Razelle Kurzrock

Faculty, Staff and Student Publications

Background: Inducible T-cell co-stimulator (ICOS) and its ligand (ICOSL) form a complex, two-faced immune machinery that can lead to both immune stimulation and inhibition.

Objective: We explored ICOS transcriptomic expression patterns and their relationship with other checkpoints and with outcomes in patients with advanced/metastatic cancers.

Design: This was a retrospective cohort study.

Methods: RNA expression for ICOS and other immune checkpoints was quantified by RNA sequencing and stratified by rank values into high (75-100 percentiles) and low (0-24 percentiles). Fischer's exact tests were used for univariate analyses to evaluate independent predictors of ICOS high and logistic regression was used for …

Isatuximab For The Treatment Of Multiple Myeloma: Current Clinical Advances And Future Directions, Paul G Richardson, Elisabeth K O'Donnell, Peter O'Gorman, Lisa B Leypoldt, Jacob Laubach, Francesca Gay, Xavier Leleu, Thierry Facon, Philippe Moreau, Meletios A Dimopoulos, Hartmut Goldschmidt, Elias K Mai, Michele Cavo, Katja C Weisel, Jesus G Berdeja, Robert Z Orlowski, Meral Beksaç, Aurore Perrot, Joseph Mikhael, Thomas Martin

Faculty, Staff and Student Publications

Introduction: The addition of the anti-CD38 monoclonal antibody isatuximab to standard therapies is transforming the care of patients with newly diagnosed multiple myeloma (NDMM), as previously seen in the relapsed/refractory setting. This is particularly important for patients with NDMM as early treatment with effective, well tolerated therapies may ensure better clinical outcomes.

Areas covered: Here, we examine recent results from pivotal Phase 3 and 2 clinical trials that demonstrate efficacy and safety of isatuximab across multiple combinations, for both transplant-ineligible and transplant-eligible NDMM patients. We then evaluate long-term outcomes from the IKEMA and ICARIA-MM trials as well as real-world evidence …

Models And Mechanisms Of Post-Stroke Dementia And Cognitive Impairment, Romeesa Khan, Patrick Devlin, Akihiko Urayama, Rodney M Ritzel

Faculty, Staff and Student Publications

Stroke is a leading cause of death and disability globally, with significant long-term impacts such as post-stroke cognitive impairment (PSCI). PSCI affects up to one-third of stroke survivors, substantially increasing their risk of dementia, especially after recurrent strokes. Despite advances in acute stroke treatments, the mechanisms underlying PSCI remain poorly understood. Emerging evidence highlights that PSCI arises from a complex interplay of vascular damage, neurodegenerative pathologies, and chronic inflammation. This review explores the epidemiology and clinical characteristics of PSCI, emphasizing the role of age, education, vascular integrity, and comorbidities such as diabetes. Additionally, we examine experimental findings that utilize rodent …

New Insights Into The Mechanisms Of Electroconvulsive Therapy In Treatment-Resistant Depression, Ana C Ruiz, Abdul Haseeb, William Baumgartner, Edison Leung, Giselli Scaini, Joao Quevedo

Faculty, Staff and Student Publications

Electroconvulsive therapy (ECT) remains one of the most effective interventions for treatment-resistant depression (TRD), particularly in cases involving severe symptomatology, suicidality, or psychotic features. Despite advancements aimed at enhancing the safety and cognitive tolerability of ECT, concerns about cognitive side effects continue to limit its broader acceptance. A deeper understanding of the mechanisms underlying ECT is therefore critical for refining its use and maximizing clinical outcomes. Through a narrative review of recent literature, this paper synthesizes current evidence comparing the efficacy of ECT, ketamine, and repetitive transcranial magnetic stimulation (rTMS) in the treatment of TRD. Then, the review delves into …

The Role Of Speech And Language Therapists (Slts) In International Stroke Teams: A Systematic Review, Marina Charalambous, John E Pierce, Georgia Pastou, Erasmia Kola, Sean I Savitz

Faculty, Staff and Student Publications

Background: Current published guidelines suggest that speech and language therapists (SLTs) should be part of stroke teams, but their involvement and roles according to country income are unknown.

Aims: This review aims to (1) investigate the level of involvement of SLTs in acute stroke management, rehabilitation, and long-term care, and (2) examine whether the roles and contributions of SLTs in stroke care vary according to a country's income level.

Methods: A systematic review methodology was conducted by an expert librarian and three independent researchers based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This systematic review …

Analyzing Pain Patterns In Stroke Survivors In Outpatient Clinics: A Retrospective, Cross-Sectional, Observational Study, Deniz Dishman, Catherine Gonzalez, Tia S Thomas, Hari Kishan Indupuru, Seokhun Kim, Charles Green, Anjail Sharrief, Sean I Savitz

Faculty, Staff and Student Publications

Background: Pain is one of the most common sequelae after a stroke. Yet it is under-recognized, under-treated, and under-investigated, with no standard care guidelines for management during post-stroke recovery.

Purpose: The primary objective of this study was to capture the prevalence of pain and different pain types in stroke survivors.

Patients and methods: The study included stroke survivors who completed a pre-visit telehealth review of systems instrument between March 1, 2020, and February 28, 2022. 442 out-patient subjects were identified and matched to their respective electronic health record from the incident stroke. Subjects were divided into pain and no-pain groups …

Novel Use And Value Of Contrast-Enhanced Susceptibility-Weighted Imaging Morphologic And Radiomic Features In Predicting Extremity Soft Tissue Undifferentiated Pleomorphic Sarcoma Treatment Response, Raul F Valenzuela, Elvis De Jesus Duran Sierra, Mathew A Canjirathinkal, Behrang Amini, Ken-Pin Hwang, Jingfei Ma, Keila E Torres, R Jason Stafford, Wei-Lien Wang, Robert S Benjamin, Andrew J Bishop, John E Madewell, William A Murphy, Colleen M Costelloe

Faculty, Staff and Student Publications

Purpose: Undifferentiated pleomorphic sarcomas (UPSs) demonstrate therapy-induced hemosiderin deposition, granulation tissue formation, fibrosis, and calcification. We aimed to determine the treatment-assessment value of morphologic tumoral hemorrhage patterns and first- and high-order radiomic features extracted from contrast-enhanced susceptibility-weighted imaging (CE-SWI).

Materials and methods: This retrospective institutional review board-authorized study included 33 patients with extremity UPS with magnetic resonance imaging and resection performed from February 2021 to May 2023. Volumetric tumor segmentation was obtained at baseline, postsystemic chemotherapy (PC), and postradiation therapy (PRT). The pathology-assessed treatment effect (PATE) in surgical specimens separated patients into responders (R; ≥90%, n = 16), partial responders …

Ai/Ml-Empowered Approaches For Predicting T Cell-Mediated Immunity And Beyond, Cheng-Chi Chao, Yulun Chiu, Lucas Yeung, Cassian Yee, Chongming Jiang, Xiling Shen

Faculty, Staff and Student Publications

T cells play a dual role in various physiopathological states, capable of eliminating tumors and infected cells, while also playing a pathogenic role when activated by autoantigens, causing self-tissue damage. The regulation of T cell-peptide/major histocompatibility complex (TCR-pMHC) recognition is crucial for maintaining disease balance and treating cancer, infections, and autoimmune diseases. Despite efforts, predictive models of TCR-pMHC specificity are still in the early stages. Inspired by advances in protein structure prediction via deep neural networks, we evaluated AlphaFold 3 (AF3)-based AI computation as a method to predict TCR epitope specificity. We demonstrate that AlphaFold can model TCR-pMHC interactions, distinguishing …

Correspondence To Letter To The Editor On “Genomic Biomarkers To Predict Response To Atezolizumab Plus Bevacizumab Immunotherapy In Hepatocellular Carcinoma: Insights From The Imbrave150 Trial”, Sung Hwan Lee, Sun Young Yim, Ji Hoon Kim, Sunyoung S Lee, Ahmed O Kaseb, Peng Wei, Ju-Seog Lee

Faculty, Staff and Student Publications

No abstract provided.

Correction: New Insights Into The Mechanisms Of Electroconvulsive Therapy In Treatment-Resistant Depression, Ana C Ruiz, Abdul Haseeb, William Baumgartner, Edison Leung, Giselli Scaini, Joao Quevedo

Faculty, Staff and Student Publications

This corrects the article "New insights into the mechanisms of electroconvulsive therapy in treatment-resistant depression", 1614076.

The Impact Of A Small-Group Mammography Video Discussion On Promoting Screening Uptake Among Nonadherent Chinese American Immigrant Women: A Randomized Controlled Trial, Naomi Q P Tan, Grace X Ma, Annette E Maxwell, Roger L Brown, Kathy Zhou, Alice Loh, Lucy Young, Robert J Volk, Qian Lu, Judy Huei-Yu Wang

Faculty, Staff and Student Publications

Background: The objective of this study was to evaluate the efficacy of an in-person, small-group mammography video discussion (SMVD) intervention on mammography uptake among nonadherent Chinese American immigrant women.

Methods: Women (N = 956) were randomized into either an SMVD group, where Chinese-speaking community health workers (CHWs) used an effective, culturally appropriate video to discuss mammography, or a video-only group, which viewed the cultural video sent by mail. Outcomes were mammography uptake at 6 months and 21 months postintervention.

Results: Women in both groups increased mammography uptake, and an outcome analysis revealed no group differences (adjusted odds ratio [AOR], 1.18; …

Building Boundary-Crossers In Clinical-Translational Research: An Exploratory Study Of A Novel Communication Intervention, Carrie Cameron, Irene Rull-Garcia, Laura G Meyer, Jose-Armando Fernandez-Guerrero, Erin K Dahlstrom, Christine Bell, Christine Pribbenow

Faculty, Staff and Student Publications

INTRODUCTION: Integrating scientific research across multiple disciplines to advance breakthroughs is at the heart of clinical-translational science (CTS); among competencies that have been identified as essential for progress, skillful communication is critical. Few tools are available to address the social dynamics of the multidimensional diversity characteristics of CTS. We created the "Building a Diverse Biomedical Workforce Through Communication Across Difference (CAD)" workshop intervention. Based on principles of intercultural communication, CAD taught novel situationally-based communication skills to dyads of near-peer mentors and their undergraduate mentees. This study reports on the effectiveness of the operative mechanisms employed in CAD workshops for helping …

Tissue And Imaging Biomarkers Of Response To Neoadjuvant Nivolumab Or Nivolumab Plus Ipilimumab In Patients With Resectable Hepatocellular Carcinoma, Michael Lapelusa, Shadi Chamseddine, Hop Sanderson Tran Cao, Lianchun Xiao, Elshad Hasanov, Priya Bhosale, Hesham M Amin, Yehia I Mohamed, Betul Gok Yavuz, Yara Sakr, Li Xu, Ian Hu, Sunyoung S Lee, Divya Sakamuri, Sonali Jindal, Van Nguyen, Michael A Curran, Ryan Sun, Asif Rashid, Dan Gabriel Duda, Padmanee Sharma, Aliya Qayyum, Ahmed Omar Kaseb

Faculty, Staff and Student Publications

Introduction: Perioperative immunotherapy has shown promise in some patients with early-stage hepatocellular carcinoma (HCC). This study examined tissue and imaging biomarkers associated with pathologic response in a phase II clinical trial in patients with resectable HCC.

Methods: Analysis included 18 patients with biopsy-proven resectable HCC treated with neoadjuvant nivolumab plus ipilimumab or nivolumab alone in a phase II clinical trial at MD Anderson Cancer Center (NCT03222076). Liver MRE (to measure tissue fibrosis) and biopsies (to evaluate immune activation markers) were obtained serially pretreatment and after completing neoadjuvant immunotherapy. A major pathologic response (MPR) was defined as tumor necrosis …

Characterizing Spatial Immune Architecture In Metastatic Melanoma Using High-Dimensional Multiplex Imaging, Joel Eliason, Santhoshi Krishnan, Yasunari Fukuda, Matias A Bustos, Dan Winkowski, Sungnam Cho, Akshay Basi, Regan Baird, Elizabeth A Grimm, Michael A Davies, Dave S B Hoon, Arvind Rao, Jared K Burks, Suhendan Ekmekcioglu

Faculty, Staff and Student Publications

Introduction: Immune checkpoint inhibitors (ICIs) have significantly improved survival for patients with metastatic melanoma, yet many experienceresistance due to immunosuppressive mechanisms within the tumor immune microenvironment (TIME). Understanding how the spatial architecture of immune and inflammatory components changes across disease stages may reveal novel prognostic biomarkers and therapeutic targets.

Methods: We performed high-dimensional spatial profiling of two melanoma tissue microarrays (TMAs), representing Stage III (n = 157) and Stage IV (n = 248) metastatic tumors. Using imaging mass cytometry (IMC) and multiplex immunofluorescence (mIF), we characterized the phenotypic, functional, and spatial properties of the TIME. Cellular neighborhoods were …

Case Report: Durable Remission After Abscopal Effect Following Transcatheter Hepatic Arterial Embolization In A Patient With Mucosal Melanoma Refractory To Immunotherapy, Lynsey M Claus, Hannah E Kostan, Marshall E Hicks, Rony Avritscher, Michael A Davies

Faculty, Staff and Student Publications

Mucosal melanoma, a rare subtype of melanoma affecting mucosal surfaces, presents significant challenges in diagnosis and treatment, particularly due to its low programmed death-ligand 1 (PD-L1) expression and reduced response to immune checkpoint inhibitors (ICIs). This case report describes a 58-year-old woman with metastatic nasal mucosal melanoma initially resistant to neoadjuvant ipilimumab and nivolumab. After undergoing hepatic transcatheter arterial embolization, she experienced an unexpected abscopal effect, where distant metastases showed near-complete resolution despite prior lack of response to immunotherapy. The patient's disease initially progressed despite two cycles of ICI treatment, and further immunotherapy with nivolumab and relatimab did not improve …

Editorial: Molecular Mechanisms And Targeted Therapies For Colorectal Cancer Vol Ii, Alessandro Passardi, David Gibbons, Antonio Mario Scanu, Shilpa S Dhar

Faculty, Staff and Student Publications

No abstract provided.

The Impact Of Post-Remission Granulocyte Colony-Stimulating Factor Use In The Phase 3 Studies Of Venetoclax Combination Treatments In Patients With Newly Diagnosed Acute Myeloid Leukemia, Courtney D Dinardo, Keith W Pratz, Panayiotis Panayiotidis, Xudong Wei, Vladimir Vorobyev, Árpád Illés, Inho Kim, Vladimir Ivanov, Grace Ku, Catherine L Miller, Meng Zhang, Fernando Tatsch, Jalaja Potluri, Xenia Schmidt, Christian Récher

Faculty, Staff and Student Publications

No abstract provided.

Head And Neck Gross Tumor Volume Automatic Segmentation Using Pocketnet, Awj Twam, Adrian Celaya, Evan Lim, Khaled Elsayes, David Fuentes, Tucker Netherton

Faculty, Staff and Student Publications

Head and neck cancer (HNC) represents a significant global health burden, often requiring complex treatment strategies, including surgery, chemotherapy, and radiation therapy. Accurate delineation of tumor volumes is critical for effective treatment, particularly in MR-guided interventions, where soft tissue contrast enhances visualization of tumor boundaries. Manual segmentation of gross tumor volumes (GTV) is labor intensive, time-consuming and prone to variability, motivating the development of automated segmentation techniques. Convolutional neural networks (CNNs) have emerged as powerful tools in this task, offering significant improvements in speed and consistency. In this study, we participated as Team Pocket in Task 1 of the HNTS-MRG …

Meeting Highlights The 4th Marie Skłodowska-Curie Symposium On Cancer Research And Care: Mechanisms Of Support For Regional & International Collaborations, Pawel Kalinski, Kathleen M Kokolus, Indu Ahluwalia, Mihaela Balu, Łukasz Balwicki, Brygida Baran, Loretta Beine, Mikhail Berezin, Ioana Berindan-Neagoe, Andriy Beznosenko, Blanka Borowiec, Szabolcs Bozsányi, Jonathan Bramson, Brian Czerniecki, Rūta Everatt, Wojciech Fendler, Peter Forsyth, Jeffrey E Gershenwald, Maciej Goniewicz, Khurshid Guru, Andrew Hyland, Smitha James, Iva Kirac, Pawel Koczkodaj, Leszek Kotula, Maciej Łuba, Iwona Ługowska, Elizabeth Luke, Cristian Lungulescu, Sandro Matosevic, Kaushal Nanavati, Michael Nemeth, Karolina Nowak, Katia Noyes, Mark Parascandola, Waldemar Priebe, Piotr Rutkowski, Mukund Seshadri, Christine E Sheffer, Ioana-Miruna Stanciu, Joanna Stanson, Telisa Stewart, Edita Sužiedėlienė, Kęstutis Sužiedėlis, Iryna Tanasiichuk, Anda M Vlad, Wei-Zen Wei, Dylan Williams, Malgorzata Wojtowicz, Tomasz Zdrojewski

Faculty, Staff and Student Publications

The Marie Skłodowska-Curie Symposia on Cancer Research and Care (MSCS-CRC) promote collaborations between cancer researchers and care providers in the United States, Canada and Central and Eastern European Countries (CEEC) to accelerate the development of new cancer therapies, new strategies for early detection and prevention, and improve cancer care and the quality of life for patients and their families. The 4th MSCS-CRC (September 25-27, 2024, Buffalo, New York) brought together 147 participants from the US, Canada, Croatia, Czechia, Lithuania, Poland, Romania and Ukraine, and involved representatives of the US Centers for Disease Control and Prevention (CDC), National Cancer Institute (NCI) …

Cord Blood-Derived Ink T Cells As A Platform For Allogeneic Car T Cell Therapy, Maison Grefe, Abel Trujillo-Ocampo, Jelita Clinton, Hong He, Ling Yu, Dan Li, Qing Ma, Elizabeth J Shpall, Jeffrey J Molldrem, Jin S Im

Faculty, Staff and Student Publications

CD1d-restricted invariant Natural Killer (iNK) T cells are a suitable candidate for allogeneic Chimeric Antigen Receptor (CAR) T cell therapy as they do not cause graft-versus-host disease (GvHD) due to the monomorphic nature of CD1d proteins. However, the phenotypic and functional heterogeneity of iNK T cells from adult donors (AD) may lead to the inconstant CAR-iNK T cell products. Cord blood-derived (CB) iNK T cells, in contrast, exhibit inter-donor homogeneity in phenotype including uniform CD4 expression and are enriched in memory iNK T cell populations. Thus, we evaluated the preclinical therapeutic potential of iNK T cells derived from cord blood …

Stat3 Inhibition In Combination With Cd47 Blockade Inhibits Osteosarcoma Lung Metastasis, Pradeep Shrestha, Rejeena Shrestha, You Zhou, Rafal Zielinski, Waldemar Priebe, Eugenie S Kleinerman

Faculty, Staff and Student Publications

Background: New therapies are urgently needed for patients with osteosarcoma (OS). STAT3 and CD47 are potential therapeutic target in OS. Here we investigated the therapeutic activity of the orally bioavailable STAT3 inhibitor, WP1066, and anti-CD47 antibody using OS mouse models.

Methods: Cytotoxic effect of WP1066 against OS cell lines and its immunomodulatory effects were evaluated in vitro. Experimental metastasis and orthotopic syngeneic mouse models were used to investigate the therapeutic efficacy of WP1066 and anti-CD47 antibody. Further flow cytometric analysis was performed.

Results: STAT3 was constitutively activated in multiple human and mouse OS cell lines. WP1066 suppressed STAT3 activation …

Evaluation Of Quantum Contouring Algorithms For Treatment Planning On Mr Abdominal Images, Rachel Glenn, Tucker Netherton, Adrian Celaya, Mohamed Eltaher, Beatrice Riviere, Eugene J Koay, David Fuentes

Faculty, Staff and Student Publications

Introduction: Quantum computing is increasingly being investigated for integration into medical radiology and healthcare applications worldwide. Given its potential to enhance clinical care and medical research, there is growing interest in evaluating its practical applications in clinical workflows.

Methods: We developed an evaluation of quantum computing-based auto-contouring methods to introduce medical physicists to this emerging technology. We implemented existing quantum algorithms as prototypes tailored for specific quantum hardware, focusing on their application to auto-contouring in medical imaging. The evaluation was performed using a medical resonance imaging (MRI) abdominal dataset, comprising 102 patient scans.

Results: The quantum algorithms were applied to …

Head-To-Head Comparison Of Aptamer- And Antibody-Based Proteomic Platforms In Human Cerebrospinal Fluid Samples From A Real-World Memory Clinic Cohort, Raquel Puerta, Amanda Cano, Pablo García-González, Fernando García-Gutiérrez, Maria Capdevila, Itziar De Rojas, Clàudia Olivé, Josep Blázquez-Folch, Oscar Sotolongo-Grau, Andrea Miguel, Laura Montrreal, Pamela Martino-Adami, Asif Khan, Adelina Orellana, Yun Ju Sung, Ruth Frikke-Schmidt, Natalie Marchant, Jean Charles Lambert, Maitée Rosende-Roca, Montserrat Alegret, Maria Victoria Fernández, Marta Marquié, Sergi Valero, Lluís Tárraga, Carlos Cruchaga, Alfredo Ramírez, Mercè Boada, Bart Smets, Alfredo Cabrera-Socorro, Agustín Ruiz

Faculty, Staff and Student Publications

High-throughput proteomic platforms are crucial to identify novel Alzheimer’s disease (AD) biomarkers and pathways. In this study, we evaluated the reproducibility and reliability of aptamer-based (SomaScan® 7k) and antibody-based (Olink® Explore 3k) proteomic platforms in cerebrospinal fluid (CSF) samples from the Ace Alzheimer Center Barcelona real-world cohort. Intra- and inter-platform reproducibility were evaluated through correlations between two independent SomaScan® assays analyzing the same samples, and between SomaScan® and Olink® results. Association analyses were performed between proteomic measures, CSF biological traits, sample demographics, and AD endophenotypes. Our 12-category metric of reproducibility combining correlation analyses identified 2428 highly reproducible SomaScan CSF measures, …

Linking Transcriptome And Morphology In Bone Cells At Cellular Resolution With Generative Ai, Lu Lu, Noriaki Ono, Joshua D Welch

Faculty, Staff and Student Publications

Recent advancements in deep learning (DL) have revolutionized the capability of artificial intelligence (AI) by enabling the analysis of large-scale, complex datasets that are difficult for humans to interpret. However, large amounts of high-quality data are required to train such generative AI models successfully. With the rapid commercialization of single-cell sequencing and spatial transcriptomics platforms, the field is increasingly producing large-scale datasets such as histological images, single-cell molecular data, and spatial transcriptomic data. These molecular and morphological datasets parallel the multimodal text and image data used to train highly successful generative AI models for natural language processing and computer vision. …

Dynamic And Concordance-Assisted Learning For Risk Stratification With Application To Alzheimer’S Disease, Wen Li, Ruosha Li, Ziding Feng, Jing Ning

Faculty, Staff and Student Publications

Dynamic prediction models capable of retaining accuracy by evolving over time could play a significant role for monitoring disease progression in clinical practice. In biomedical studies with long-term follow up, participants are often monitored through periodic clinical visits with repeat measurements until an occurrence of the event of interest (e.g. disease onset) or the study end. Acknowledging the dynamic nature of disease risk and clinical information contained in the longitudinal markers, we propose an innovative concordance-assisted learning algorithm to derive a real-time risk stratification score. The proposed approach bypasses the need to fit regression models, such as joint models of …

Disruption Of Distal Appendage Protein Cep164 Causes Skeletal Malformation In Mice, Hiroyuki Yamaguchi, Megumi Kitami, Margaret Li, Sowmya Swaminathan, Radbod Darabi, Ken-Ichi Takemaru, Yoshihiro Komatsu

Faculty, Staff and Student Publications

The primary cilium is a cellular antenna to orchestrate cell growth and differentiation. Deficient or dysfunctional cilia are frequently linked to skeletal abnormalities. Previous research demonstrated that ciliary proteins regulating axoneme elongation are essential for skeletogenesis. However, the role of the ciliary proteins responsible for initiating cilium assembly in skeletal development remains unknown. Here, we investigate the function of centrosomal protein of 164 kDa (CEP164), a key ciliogenesis regulator that localizes at the distal appendages of the mother centriole, during skeletal development in mice. Interestingly, the mesodermal cell-specific Cep164 deletion resulted in severe bone defects and osteoblast-specific deletion of Cep164 …

Transcriptomic Profile Analysis Of Brain Tissue In The Absence Of Functional Trpm8 Calcium Channel, Erick B Saldes, Alexandra Erdmier, Jai Velpula, Timothy E Koeltzow, Michael X Zhu, Swapna Asuthkar

Faculty, Staff and Student Publications

Background/Objectives: Transient Receptor Potential Melastatin 8 (TRPM8) is a non-selective, Ca2+-permeable cation channel involved in thermoregulation and other physiological processes, such as basal tear secretion, cell differentiation, and insulin homeostasis. The activation and deactivation of TRPM8 occur through genetic modifications, channel interactions, and signaling cascades. Recent evidence suggests a significant role of TRPM8 in the hypothalamus and amygdala related to pain sensation and sexual behavior. Notably, TRPM8 has been implicated in neuropathic pain, migraines, and neurodegenerative diseases such as Parkinson's disease. Our laboratory has identified testosterone as a high-affinity ligand of TRPM8. TRPM8 deficiency appears to influence behavioral traits in …

Double-Blind Randomised Trial Of Saline Solution For Gargling And Nasal Rinsing In Sars-Cov-2 Infection, Sebastian R Espinoza, Lexton Trauffler, Amir Shamshirsaz, Alireza Shamshirsaz, Andres Espinoza, Jimmy Espinoza, Alice O'Brien

Faculty, Staff and Student Publications

Background: Previous studies have shown that hypertonic saline nasal irrigation and gargling reduced the duration of symptoms in upper respiratory infections caused by coronavirus. This study aims to investigate the effects of two saline regimens on symptoms associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).

Methods: Between 2020 and 2022, individuals aged 18-65 years who tested positive for SARS-CoV-2 infection via polymerase chain reaction (PCR) were randomly assigned to either low- or high-saline regimens for 14 days. The low-saline solutions contained 2.13 g of salt dissolved in eight ounces of warm water, while the high-saline solution contained six grams of …

The Win Ratio Approach In Bayesian Monitoring For Two-Arm Phase Ii Clinical Trial Designs With Multiple Time-To-Event Endpoints, Xinran Huang, Jian Wang, Jing Ning

Faculty, Staff and Student Publications

To assess the preliminary therapeutic impact of a novel treatment, futility monitoring is commonly employed in Phase II clinical trials to facilitate informed decisions regarding the early termination of trials. Given the rapid evolution in cancer treatment development, particularly with new agents like immunotherapeutic agents, the focus has often shifted from objective response to time-to-event endpoints. In trials involving multiple time-to-event endpoints, existing monitoring designs typically select one as the primary endpoint or employ a composite endpoint as the time to the first occurrence of any event. However, relying on a single efficacy endpoint may not adequately evaluate an experimental …

Bayesian Nonparametric Model For Heterogeneous Treatment Effects With Zero-Inflated Data, Chanmin Kim, Yisheng Li, Ting Xu, Zhongxing Liao

Faculty, Staff and Student Publications

One goal of precision medicine is to develop effective treatments for patients by tailoring to their individual demographic, clinical, and/or genetic characteristics. To achieve this goal, statistical models must be developed that can identify and evaluate potentially heterogeneous treatment effects in a robust manner. The oft-cited existing methods for assessing treatment effect heterogeneity are based upon parametric models with interactions or conditioning on covariate values, the performance of which is sensitive to the omission of important covariates and/or the choice of their values. We propose a new Bayesian nonparametric (BNP) method for estimating heterogeneous causal effects in studies with zero-inflated …