Genetic Phenomena Commons^™

Surgical And Blood-Based Minimal Residual Disease In Patients With Ovarian Cancer After First-Line Therapy: Clinical Outcomes And Translational Opportunities, Anne Knisely, Yibo Dai, Graham L Barlow, Sanghoon Lee, Barrett Lawson, Bryan Fellman, Wei Lu, Idania Carolina Lubo Julio, Rossana N Lazcano, Manoj Chelvanambi, Brenda Melendez, Bharat Singh, Bhavana Singh, Khalida Wani, Jianfeng Chen, Chih-Chen Yeh, Jianjun Gao, Sean Barnes, Ou Shi, Khaja B Khan, Alejandra G Serrano, Lorena I Gomez-Bolanos, Carly Bess Scalise, Samantha K Cheung, Punashi Dutta, Sharlene Velichko, Adam C Elnaggar, Minetta C Liu, Roni N Wilke, Jeffrey How, Lois M Ramondetta, David M Boruta, Gwyn Richardson, Aaron Shafer, Shannon N Westin, Travis Sims, Anil K Sood, Pedro T Ramirez, Alexander J Lazar, Pamela T Soliman, Karen Lu, Cara L Haymaker, Luisa M Solis Soto, Jennifer A Wargo, Rachel Grisham, Kai W Wucherpfennig, Linghua Wang, Amir A Jazaeri

Faculty, Staff and Student Publications

Purpose: Minimal residual disease (MRD) after first-line treatment of advanced-stage ovarian cancer remains a long-standing barrier to cure. We investigated the prognostic and translational value of MRD detection by second-look laparoscopy (SLL) and ctDNA at the completion of first-line therapy.

Experimental design: Patients with high-grade epithelial ovarian cancer who had a complete clinical response to first-line therapy and underwent SLL and plasma collection for ctDNA were included. Progression-free survival (PFS) and overall survival (OS) were estimated based on MRD and clinicopathologic status. Spatial transcriptomics (GeoMx and Visium) and proteomics (CODEX) profiling were performed on serial samples from select patients.

Results: …

From Nociception In Aneural Animals To Human Suffering: Toward A Comparative Biology Of Pain, Edgar T Walters

Faculty, Staff and Student Publications

Pain is a core feature of human life, but systematic comparisons of this biological trait across taxa have been rare. A broadly accepted definition based on human experience emphasizes dual features of pain: a sensory (discriminative) component for sensing and monitoring tissue injury, and an affective (emotional) component to motivate avoidance of tissue distress. Conscious pain is coupled to unconscious nociception (detection of incipient or existing injury). This Review considers nociception and pain across phyla within a comparative framework, addressing basic questions about evolutionary origins, mechanisms and functions of pain. The occurrence of adaptive cellular responses to injury in virtually …

Mapping Cardiac Electrical Abnormalities In Rodents, Ashish Kapoor, Peter A Doris

Faculty, Staff and Student Publications

No abstract provided.

Cervical And Tumor-Associated Microbiomes In Botswana Women With And Without Hiv With Carcinoma Of The Cervix Before And After Definitive Chemoradiation, Travis T Sims, Kyoko Yoshida-Court, Molly B El Alam, Pleasure Ramatlho, Rebecca Ketlametswe, Erle S Robertson, Lauren E Colbert, Ann H Klopp, Surbhi Grover

Faculty, Staff and Student Publications

Purpose: Cervical cancer remains a significant public health concern globally and particularly in sub-Saharan Africa, where high rates of HIV infection exacerbate cervical cancer incidence. Understanding the cervical microbiome and its role in cancer progression is essential, especially in regions where both cervical cancer incidence and HIV prevalence are high. This study aimed to characterize the cervical microbiome in women living with HIV (WLWH) and HIV-negative women with squamous cell carcinoma of the cervix in Botswana, compare the microbiome between before and after chemoradiation therapy (CRT) in WLWH, and assess the prognostic value of specific microbial taxa for overall survival …

Multi-Institution Analysis Of Tarlatamab For The Treatment Of Egfr-Mutant Transformed Small Cell Lung Cancer, Alissa J Cooper, Benjamin Herzberg, Mitchell Parma, Kaiwen Wang, Laura Alder, Tejas Patil, Sonam Puri, Anjali Saqi, Phoebe Clark, Carl M Gay, Tina Cascone, Eric K Singhi, George Blumenschein, Ferdinandos Skoulidis, Janet Tu, Thomas E Stinchcombe, Charles M Rudin, Catherine A Shu, Lauren A Byers, Helena Yu, Bingnan Zhang

Faculty, Staff and Student Publications

No abstract provided.

A Comparative Study Of Clinically Used Fast Monte Carlo Dose Engines For Proton Therapy, Sherif M Gadoue, Narayan Sahoo

Faculty, Staff and Student Publications

Background: Several fast Monte Carlo (MC) codes have been implemented and used to simulate proton transport and calculate patient doses in proton therapy. The resulting dose is typically compared to full MC codes, rather than other fast MC codes.

Purpose: The primary goal of this study was to compare the gamma pass rates (GPRs) of dose calculation from different fast MC codes to evaluate the accuracy of the computation and modeling among these codes.

Methods: Two GPU codes and one CPU MC code were commissioned to model our clinical proton beamline at University of Texas MD Anderson Cancer Center. The …

Multiomic Random Forest Toxicity Modeling Of Radiation Esophagitis, Saurabh S Nair, Ramon M Salazar, Ting Xu, Alexandra O Leone, Zhongxing Liao, Joshua S Niedzielski

Faculty, Staff and Student Publications

Background and purpose: Radiation esophagitis (RE) is a major dose-limiting toxicity resulting from radiotherapy for non-small-cell lung cancer (NSCLC). Multiomic features may provide additional predictive value for high-grade RE compared to traditionally used clinical and dose-volume histogram (DVH) parameters. We aimed to investigate the utility of multiomic features in improving RE toxicity prediction models.

Materials and methods: Of the 179 NSCLC patients considered, 27 patients (15.08 %) were found to have toxicity ≥grade 3 RE per CTCAE v5.0. A total of 343 CT- and PET- based radiomic and dosiomic features were extracted. Four toxicity prediction models were created using clinical …

Evaluating Dimensionality Reduction For Patient-Reported Outcome-Based Survival Modeling In Patients With Head And Neck Cancer, Eric Ababio Anyimadu, Yaohua Wang, Amy C Moreno, Clifton David Fuller, Xinhua Zhang, Guadalupe M Canahuate

Faculty, Staff and Student Publications

Purpose: This study aims to improve survival modeling in head and neck cancer (HNC) by integrating patient-reported outcomes (PROs) using dimensionality reduction techniques. PROs capture symptom severity across the treatment timeline and offer key insights for personalized care. However, their high dimensionality poses challenges such as overfitting and computational complexity. This work focuses on transforming and incorporating PRO data to enhance model performance in HNC.

Materials and methods: We analyzed retrospective data of 923 patients with HNC treated at the University of Texas MD Anderson Cancer Center between 2010 and 2021. Baseline clinical data including demographic, treatment, and disease characteristics …

Imaging- And Tumor Biomarker-Based Multivariable Model For Early Prediction Of Pathologic Complete Response To Neoadjuvant Systemic Therapy In Triple-Negative Breast Cancer, Beatriz E Adrada, Mary S Guirguis, Lei Huo, Clinton Yam, Debu Tripathy, Wei Yang, Tanya Moseley, Gary J Whitman, Jessica W T Leung, Huong Le-Petross, Deanna L Lane, Nour Abuhadra, Jennifer Litton, Vicente Valero, Kelly K Hunt, Banu Arun, Rania Mohamed, Jia Sun, Anil Korkut, Sanaz Pashapoor, Jason White, Alastair Thompson, Peng Wei, Jingfei Ma, Stacy Moulder, Gaiane M Rauch

Faculty, Staff and Student Publications

Purpose: The response of triple-negative breast cancer (TNBC) to neoadjuvant therapy (NAT) varies widely. This study aimed to determine the performance of clinicopathologic biomarkers and volumetric changes on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting pathologic complete response (pCR) to NAT in patients with TNBC.

Patients and methods: This study included 264 patients with stage I to III TNBC enrolled in a prospective clinical trial. These patients underwent DCE-MRI at baseline and after two and/or after four cycles of dose-dense anthracycline and cyclophosphamide. Tumor volume (TV) was calculated by measuring three tumor dimensions at each time point. Clinicopathologic markers …

Cancer-Associated Fibroblasts As Mediators Of Tissue Microenvironment Remodeling In Cancer, Fernanda G Kugeratski, Emily J Kay, Sara Zanivan

Faculty, Staff and Student Publications

Cancer-associated fibroblasts (CAFs) are a multifunctional cell population of solid tumors that substantially remodel the tumor microenvironment (TME). The combination of single-cell and spatial technologies with elegant mouse models and analysis of patient samples is enabling unprecedented advances in the characterization of CAF origins, heterogeneity, and functions within the TME. As such, the field is now evolving to delineate tissue-specific subpopulations of CAFs, their markers, and the biological context in which each subset presents with a tumor-promoting or a tumor-restraining function. In this timely review, we discuss recent advances in CAF biology in the context of emerging areas of interest …

Spherical Wave Expansion Coefficients For Radiation From A Planar Velocity Source, Blake E Simon, Mark F Hamilton

Faculty, Staff and Student Publications

A general theory for obtaining spherical wave function expansion coefficients for a sound beam transmitted by a planar velocity source is presented. By neglecting evanescent wave components and thus making the proposed method only approximate in the near field, it is shown that these coefficients can be obtained for any expansion point using just the normal velocity condition in the source plane. Additionally, simplifications are presented for axisymmetric sources. Results are compared with direct numerical evaluation of the Rayleigh integral for source conditions corresponding to a circular and rectangular piston. The present theory can be used in calculations of acoustic …

Ideate-Lung02: A Phase 3 Study Of Second-Line Ifinatamab Deruxtecan In Patients With Relapsed Small Cell Lung Cancer, Taofeek K Owonikoko, Lauren Byers, Ying Cheng, Hidetoshi Hayashi, Luis Paz-Ares, Haichuan Hu, Cecilio Roi Garcia, Juliette Godard, Mei Tang, Charles M Rudin

Faculty, Staff and Student Publications

Patients with small cell lung cancer (SCLC) have poor prognosis and limited treatment options beyond first-line therapy. B7 homolog 3 (B7-H3) is minimally expressed in normal tissues but highly expressed in SCLC. Ifinatamab deruxtecan (I-DXd), a B7-H3-directed antibody-drug conjugate, has demonstrated promising efficacy and a manageable safety profile in various tumours, including SCLC. IDeate-Lung02 is a global, randomized, open-label Phase 3 study of ~540 patients with relapsed SCLC. Adults with one prior line of platinum-based systemic therapy, ECOG performance status 0-1, and ≥1 measurable lesion (per RECIST 1.1) are eligible for study participation. Patients with asymptomatic untreated or previously treated …

Herthena-Pantumor01: A Phase Ii Study Of Patritumab Deruxtecan (Her3-Dxd) In Previously Treated Advanced Solid Tumors, Thomas Powles, Aarti Bhatia, Barbara Burtness, Takahiro Kogawa, Tomohiro Nishina, Christos Fountzilas, Meredith Mckean, Funda Meric-Bernstam, Nicoletta Colombo, James W Smithy, Jérome Fayette, Sunandana Chandra, David W Sternberg, Fan Jin, Kendall Sullivan, Sue Yueh, Graham Clinthorne, Ariel E Aguilo, Ragini Kudchadkar, Hidetoshi Hayashi

Faculty, Staff and Student Publications

Human epidermal growth factor receptor 3 (HER3) is a receptor tyrosine kinase that is expressed in numerous solid tumors. Higher levels of HER3 expression in multiple tumor types are associated with adverse clinical outcomes, such as reduced survival. However, there is currently no HER3-directed antibody-drug conjugate approved for the treatment of any cancer. Improved treatment options are needed, in particular for patients who progress on standard therapies. HER3-DXd is an investigational HER3-directed antibody-drug conjugate composed of an anti-HER3 monoclonal antibody linked to a topoisomerase I inhibitor payload via a stable tetrapeptide-based cleavable linker. In previous clinical trials, HER3-DXd demonstrated a …

Isoform-Level Analyses Of 6 Cancers Uncover Extensive Genetic Risk Mechanisms Undetected At The Gene-Level, Yung-Han Chang, Sean T Bresnahan, S Taylor Head, Tabitha A Harrison, Yao Yu, Bogdan Pasaniuc, Arjun Bhattacharya

Faculty, Staff and Student Publications

Background: Integrating genome-wide association study (GWAS) and transcriptomic datasets can identify mediators for genetic risk of cancer. Traditional methods often are insufficient as they rely on total gene expression measures and overlook alternative splicing, which generates different transcript-isoforms with potentially distinct effects.

Methods: We integrate multi-tissue isoform expression data from the Genotype Tissue-Expression Project with GWAS summary statistics (all N > ~20,000 cases) to identify isoform- and gene-level associations with six cancers (breast, endometrial, colorectal, lung, ovarian, prostate) and six related cancer subtype classifications (N = 12 total).

Results: Directly modeling isoforms using transcriptome-wide association studies (isoTWAS) significantly improves discovery of …

Epigenetic Age Acceleration Mediates Treatment Effects On Cardiometabolic And Cardiovascular Risk In Childhood Cancer Survivors, Xiaoxi Meng, Tiffany Eulalio, Yoonji Kim, John Easton, Heather L Mulder, Geoffrey Neale, Kyla Shelton, Rebecca M Howell, Mengqi Xing, Sedigheh Mirzaei, Deo Kumar Srivastava, Bonnie Ky, Stephanie B Dixon, Melissa M Hudson, Kirsten K Ness, Gregory T Armstrong, Zhaoming Wang

Faculty, Staff and Student Publications

BACKGROUND: Childhood cancer survivors are at increased risk for epigenetic age acceleration (EAA) and subsequent morbidities, including cardiometabolic risk factors (CMRFs) and cardiovascular diseases, because of prior genotoxic treatments.

OBJECTIVES: The aim of this study was to evaluate the mediating role of EAA in the relationship between cancer treatment exposures and risk for CMRFs and cardiovascular diseases.

METHODS: This study included 2,939 5-year survivors from SJLIFE (St. Jude Lifetime Cohort) who underwent DNA methylation profiling using peripheral blood mononuclear cells. EAA was calculated using 3 established epigenetic clocks: DunedinPACE, PCPhenoAge, and GrimAge2. Treatment data, including body region-specific radiotherapy (RT) and …

Quantitative Evaluation Of Apparent Diffusion Coefficient In A Large Multi-Unit Institution, Joshua P Yung, Yao Ding, Ken-Pin Hwang, Carlos E Cardenas, H Asher Ai, Natalie A West, R Jason Stafford

Faculty, Staff and Student Publications

Background and purpose: Diffusion weighted imaging (DWI) and their calculated apparent diffusion coefficient (ADC) values in magnetic resonance imaging (MRI) has grown with applications across multiple anatomical sites and settings across diagnostic and oncologic therapy settings, necessitating characterizing its quantitative performance across multiple scanners. Therefore, the purpose of this study was to determine the quantitative accuracy of DWI and their calculated ADC values across a fleet of MRI systems using a NIST-traceable diffusion phantom.

Materials and methods: Three NIST/QIBA DWI phantoms were imaged with protocols provided with the phantom on a multi-vendor fleet of 23 clinical MRI scanners. User-directed regions-of-interest …

Childhood Trauma And Inflammatory Biomarker Effects On Cortical Thinning In Schizophrenia Spectrum Disorders, Samantha Narvaez, Yizhou Ma, Joshua Chiappelli, Hemalatha Sampath, Alia Warner, Giselli Scaini, L Elliot Hong

Faculty, Staff and Student Publications

Patients with schizophrenia spectrum disorders (SSD) have higher risks for early and adult life traumatic events and suffer from a heightened body response to stress and increased inflammatory activities. We hypothesize that in SSD, the effect of stress is associated with prolonged activation of the inflammatory system and causes elevation in immune markers. We examined the effects of childhood trauma and adult stressful life events on a C-reactive protein (CRP) and their combined contribution to cortical thickness thinning in 49 SSD patients and 26 healthy controls. Participants with SSD reported higher levels of childhood trauma (p = 0.015) and lifetime …

Natural History Of Primary Retroperitoneal Extra-Visceral Perivascular Epithelioid Cell Tumors (Pec): A Study From Transatlantic And Australasian Retroperitoneal Sarcoma Working Group (Tarpswg), Eyal Mor, Sameer Apte, Catherine Mitchell, Carolyn Nessim, Max Almond, Jose Antonio Gonzalez Lopez, Michael J Wagner, Aviram Nissan, Miguel Henriques Abreu, Markus Albertsmeier, Mathilda Knoblauch, Adam Barlow, Emily Z Keung, Giovanni Grignani, Jason L Hornick, Alessandro Gronchi, David E Gyorki

Faculty, Staff and Student Publications

Background: Perivascular epithelioid cell tumors (PEComa) are a rare family of mesenchymal tumors that include several subtypes. There are very limited data describing the natural history of patients with extra-visceral retroperitoneal PEComas of the retroperitoneum. The aim of this study is to describe the clinical features, treatment patterns, outcomes, and diagnostic challenges of primary extra-visceral retroperitoneal or abdominopelvic PEComa over the past decade.

Patients and methods: This is a retrospective analysis of all extra-visceral, non-renal, retroperitoneal, or abdominopelvic PEComas treated at participating centers over the past 10 years.

Results: A total of 77 patients from 13 centers were included. The …

Correction: Inflammation Mediated By Gut Microbiome Promotes Immune Suppression And Lung Adenocarcinoma Progression, Zahraa Rahal, Yuejiang Liu, Fuduan Peng, Sujuan Yang, Mohamed A Jamal, Hannah Moreno, Matthew C Wong, Matthew C Ross, Ansam Sinjab, Tieling Zhou, Minyue Chen, Inti Tarifa Reischle, Jiping Feng, Chidera Chukwuocha, Elizabeth Tang, Camille Abaya, Jamie K Lim, Cheuk Hong Leung, Heather Y Lin, Nathaniel Deboever, Jack J Lee, Boris Sepesi, Don L Gibbons, Jennifer A Wargo, Junya Fujimoto, Linghua Wang, Joseph F Petrosino, Nadim J Ajami, Robert R Jenq, Seyed Javad Moghaddam, Tina Cascone, Kristi Hoffman, Humam Kadara

Faculty, Staff and Student Publications

No abstract provided.

Site-Specific Drug Release Of Monomethyl Fumarate To Treat Oxidative Stress Disorders, Thomas D Avery, Jiahe Li, Dion J L Turner, Mohd S U Rasheed, Fisher R Cherry, Fátima Rivera-Escalera, Michael J Lacagnina, Caitlyn M Gaffney, Clarissa Aguilar, Jingxian Yu, Yang Wang, Huan Xie, Dong Liang, Andrew J Shepherd, Andrew D Abell, Peter M Grace

Faculty, Staff and Student Publications

Treatment of diseases of oxidative stress through activation of the antioxidant nuclear factor E2-related factor 2 (NRF2) is limited by systemic side effects. We chemically functionalize the NRF2 activator monomethyl fumarate to require Baeyer-Villiger oxidation for release of the active drug at sites of oxidative stress. This prodrug reverses chronic pain in mice with reduced side effects and could be applied to other disorders of oxidative stress.

Adoption Of The T2-Flair Mismatch Sign Among Radiologists: How Well Are We Doing?, F Eymen Ucisik, Shekhar Khanpara, Burak Berksu Ozkara, Ziyi Li, Rasha Alfattal, Samir A Dagher, Max Wintermark, Gregory N Fuller

Faculty, Staff and Student Publications

Background and purpose: The classic T2-FLAIR mismatch sign is a highly specific MRI feature that can aid in preoperative diagnosis of isocitrate dehydrogenase (IDH)-mutant 1p/19q noncodeleted gliomas and affect surgical planning. This study aimed to assess the real-world utilization of the T2-FLAIR mismatch sign in clinical practice, and to explore the frequencies of classic- and partial T2-FLAIR mismatch within the IDH-mutant 1p/19q noncodeleted glioma population stratified by tumor grade.

Materials and methods: This retrospective cohort study from a dedicated cancer referral center included 251 patients with IDH-mutant astrocytoma diagnosed between 2017 and 2022. Pathology reports were reviewed for eligibility for …

Refining The Utility Of Late Amniocentesis In High-Risk Pregnancies, Roni Zemet, Ronald J Wapner, Ignatia B Van Den Veyver

Duncan NRI Faculty and Staff Publications

No abstract provided.

Dynamic Rewiring Of Microrna Networks In The Brainstem Autonomic Control Circuits During Hypertension Development In The Female Spontaneously Hypertensive Rat, Alison Moss, Ankita Srivastava, Lakshmi Kuttippurathu, James S. Schwaber, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

We describe global microRNA (miRNA) changes in the central autonomic control circuits during the development of neurogenic hypertension. Using the female spontaneously hypertensive rat (SHR) and the normotensive Wistar Kyoto (WKY), we analyzed the dynamic miRNA expression changes in three brainstem regions-the nucleus of the solitary tract, caudal ventrolateral medulla, and rostral ventrolateral medulla-as a time series beginning at 8 wk of age before hypertension onset through to extended chronic hypertension. Our analysis yielded nine miRNAs that were significantly differentially regulated in all three regions between SHR and WKY over time. We collated computationally predicted gene targets of these nine …

Design And Application Of A Tau Seed Amplification Assay For Screening Inhibitors Of Tau Seeding, Damian Gorski, Haley Evans, Tyler Allison, Carla Barria, Danielle Harrison, Nicolas Mendez, Sanne Kaalund, Jonas Folke, Susana Aznar, Paul Schultz, Fei Wang, Claudio Soto

Faculty, Staff and Student Publications

Background: Tau protein aggregates are a key pathological hallmark of Alzheimer's disease (AD) and are closely associated with cognitive decline and neurodegeneration. It is proposed that tau aggregates faithfully propagate throughout the brain by self-templating their disease-associated conformation onto natively-folded tau monomers, thereby inducing their aggregation and incorporation into growing fibrils. As such, the inhibition or modulation of tau seeding and aggregation represents a viable therapeutic strategy for AD and other tauopathies.

Methods: We have recently developed seed amplification assays (SAA) for the detection and amplification of small quantities of misfolded protein aggregates in various neurodegenerative diseases. In this article, …

Improving Data-Driven Gated (Ddg) Pet And Ct Registration In Thoracic Lesions: A Comparison Of Ai Registration And Ddg Ct, Tinsu Pan, M Allan Thomas, Yang Lu, Dershan Luo

Faculty, Staff and Student Publications

Purpose: Misregistration between CT and PET can result in mis-localization and inaccurate quantification of the tracer uptake in PET. Data-driven gated (DDG) CT can correct registration and quantification but requires a radiation dose of 1.3 mSv and 1 min of acquisition time. AI registration (AIR) does not require an additional CT and has been validated to improve registration and reduce the 'banana' misregistration artifacts around the diaphragm. We aimed to compare a validated AIR and DDG CT in registration and quantification of avid thoracic lesions misregistered in DDG PET scans.

Methods: Thirty PET/CT patient data (23 with 18F-FDG, 4 with …

Current States In Understanding Oligodendroglia-Mediated Neurological Issues In Neurofibromatosis Type 1 (Nf1), Benjamin E Aghoghovwia, Cheng-En Shen, Sabiha Bano, Nandini Shyamala, Alesandra Echeandia Marrero, Samer Sharafaldin, Yuan Pan

Faculty, Staff and Student Publications

Neurofibromatosis type 1 (NF1) is among the most common neurogenetic disorders and is associated with an increased risk of developing tumors in the nervous system. Additionally, up to 80% of patients with NF1 experience neurological complications, including deficits in attention, memory, and executive function. Significant effort has been dedicated to studying how NF1 mutations autonomously dysregulate neuronal function. Increasing evidence indicates that NF1 mutations also dysregulate the oligodendroglial lineage that contributes to neurological issues in NF1. Here, we summarize our current understanding of how NF1 mutations impact the oligodendroglial lineage homeostasis and plasticity. We also discuss gaps in knowledge, potential …

Kmt2d Temporally Activates Neuronal Transcriptional Factor Genes To Mediate Cerebellar Granule Cell Differentiation, Shilpa S Dhar, Kyung-Pil Ko, Jinho Jang, Calena Brown-Abel, Tao Lin, Sharad Awasthi, Kaifu Chen, Roy V Sillitoe, Jae-Il Park, Min Gyu Lee

Duncan NRI Faculty and Staff Publications

Spatiotemporal gene expression is the fundamental feature of cellular differentiation, including neuron differentiation. The epigenetic mechanism underlying spatiotemporal gene regulation during in vivo neuron differentiation remains largely unknown. Granule cells (GCs) constitute the vast majority of neurons in the cerebellum, which contains most of neurons in the brain. Here, we show that

Comparison Of Imaging Based Single-Cell Resolution Spatial Transcriptomics Profiling Platforms Using Formalin-Fixed Paraffin-Embedded Tumor Samples, Nejla Ozirmak Lermi, Max Molina Ayala, Sharia Hernandez, Wei Lu, Khaja Khan, Idania Lubo, Katarzyna Tomczak, Sean Barnes, Jinzhuang Dou, Qingnan Liang, Rti Team, Maria Gabriela Raso, Ximing Tang, Mei Jiang, Beatriz Sanchez-Espiridion, Annikka Weissferdt, John Heymach, Jianjun Zhang, Boris Sepesi, Tina Cascone, Anne Tsao, Mehmet Altan, Reza Mehran, Don Gibbons, Ignacio Wistuba, Cara Haymaker, Ken Chen, Luisa M Solis Soto

Faculty, Staff and Student Publications

Imaging-based spatial transcriptomics (ST) is evolving as a pivotal technology in studying tumor biology and associated microenvironments. However, the strengths of the commercially available ST platforms in studying spatial biology have not been systematically evaluated using rigorously controlled experiments. We use serial 5 μm sections of formalin-fixed, paraffin-embedded surgically resected lung adenocarcinoma and pleural mesothelioma samples in tissue microarrays to compare the performance of the ST platforms (CosMx, MERFISH, and Xenium (uni/multi-modal)) in reference to bulk RNA sequencing, multiplex immunofluorescence, GeoMx, and hematoxylin and eosin staining data. In addition to an objective assessment of automatic cell segmentation and phenotyping, we …

Association Between Therapeutic Alliance And Clinical Outcomes In Virtual Telepsychiatry: A Retrospective Analysis Of Data From Talkiatry, Cheryl Person, Nathaniel David Phillips, Kartik Venkatachalam, Georgia Gaveras

Faculty, Staff and Student Publications

Background: Given the increasing demand for accessible mental health services, fully virtual telepsychiatry has become a vital component of modern health care delivery. Therapeutic alliance, the collaborative and affective bond between patients and therapists, is a well-established predictor of clinical outcomes in traditional face-to-face and teletherapy. However, the relationship between therapeutic alliance and clinical outcomes in an outpatient telepsychiatry setting remains less understood.

Objective: Our primary objective was to evaluate the relationship between therapeutic alliance and clinical outcomes for depression and anxiety in an outpatient telepsychiatry practice.

Methods: This retrospective study analyzed data from treatment-seeking adults receiving services from Talkiatry, …

Aging In Mice Alters Regionally Enriched Striatal Astrocytes, Kay E Linker, Violeta Duran-Laforet, Matthias Ollivier, Xinzhu Yu, Dorothy P Schafer

Faculty, Staff and Student Publications

Aging affects multiple organs and within the brain drives distinct molecular changes across different cell types. The striatum encodes motor behaviors that decline with age, but our understanding of how cells within the striatum change remains incomplete. Using single-cell RNA sequencing from young and aged mice we identify molecularly distinct astrocyte subtypes. We show that astrocytes change significantly with age, exhibiting downregulation of genes, reduced diversity, and a shift to more homogenous inflammatory transcriptomic profiles. By exploring where striatal astrocyte subtypes are located with single-cell resolution, we map astrocytes enriched in dorsal, medial, and ventral striatum. Age increases inflammatory marker …