Genetic Phenomena Commons^™

Cancer-Induced Nerve Injury Promotes Resistance To Anti-Pd-1 Therapy, Erez N Baruch, Frederico O Gleber-Netto, Priyadharsini Nagarajan, Xiayu Rao, Shamima Akhter, Tuany Eichwald, Tongxin Xie, Mohammad Balood, Adebayo Adewale, Shorook Naara, Hinduja N Sathishkumar, Shajedul Islam, William Mccarthy, Brandi J Mattson, Renata Ferrarotto, Michael K Wong, Michael A Davies, Sonali Jindal, Sreyashi Basu, Karine Roversi, Amin Reza Nikpoor, Maryam Ahmadi, Ali Ahmadi, Catherine Harwood, Irene Leigh, Dennis Gong, Paulino Tallón De Lara, Derrick L Tao, Tara M Davidson, Nadim J Ajami, Andrew Futreal, Kunal Rai, Veena Kochat, Micah Castillo, Preethi Gunaratne, Ryan P Goepfert, Sharia D Hernandez, Nikhil I Khushalani, Jing Wang, Stephanie S Watowich, George A Calin, Michael R Migden, Mona Yuan, Naijiang Liu, Yi Ye, William L Hwang, Paola D Vermeer, Nisha J D'Silva, Yuri L Bunimovich, Dan Yaniv, Jared K Burks, Javier Gomez, Patrick M Dougherty, Kenneth Y Tsai, James P Allison, Padmanee Sharma, Jennifer A Wargo, Jeffrey N Myers, Sebastien Talbot, Neil D Gross, Moran Amit

Faculty, Staff and Student Publications

Perineural invasion (PNI) is a well-established factor of poor prognosis in multiple cancer types1, yet its mechanism remains unclear. Here we provide clinical and mechanistic insights into the role of PNI and cancer-induced nerve injury (CINI) in resistance to anti-PD-1 therapy. Our study demonstrates that PNI and CINI of tumour-associated nerves are associated with poor response to anti-PD-1 therapy among patients with cutaneous squamous cell carcinoma, melanoma and gastric cancer. Electron microscopy and electrical conduction analyses reveal that cancer cells degrade the nerve fibre myelin sheets. The injured neurons respond by autonomously initiating IL-6- and type I interferon-mediated …

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 …

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, Maurice Pérol, Haichuan Hu, Meng Qian, 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 …

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, Urs M Weber, Tejas Patil, Utsav Joshi, 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.

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, Matthew S Ning, Erle S Robertson, Kathleen M Schmeler, 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 …

Multiomic Random Forest Toxicity Modeling Of Radiation Esophagitis, Saurabh S Nair, Ramon M Salazar, Ting Xu, Alexandra O Leone, Zhongxing Liao, Laurence E Court, 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 …

A Phase 2 Study Of Cpx-351 In Combination With Venetoclax In Patients With Newly Diagnosed High-Risk Acute Myeloid Leukemia, Wei-Ying Jen, Jennifer Croden, Emmanuel Almanza-Huante, Courtney Dinardo, Kelly Chien, Danielle Hammond, Wei Qiao, Yesid Alvarado, Lucia Masarova, Andres E Quesada, Sherry Pierce, Alex Bataller, Guillermo Garcia-Manero, Amin Alousi, Nicholas Short, Naval Daver, Farhad Ravandi, Hagop Kantarjian, Tapan M Kadia

Faculty, Staff and Student Publications

Venetoclax has been combined with intensive chemotherapy regimens in the treatment of acute myeloid leukemia (AML). We aimed to investigate the safety and efficacy of venetoclax combined with full‐dose CPX‐351 (CPX + VEN) in newly diagnosed (ND) AML. Seventeen patients with a median age of 59 years (range, 43–69) were treated; 71% had secondary AML, 47% had prior hypomethylating agent (HMA) exposure, 59% had myelodysplastic syndrome (MDS)‐related (MR) mutations, 47% had complex karyotype, and 29% were TP53 mutated. The overall response rate (ORR) was 82% (95% CI, 57–96) with a composite complete remission rate (CRc) of 71% (95% CI, 50–93). …

Multiplexed Imaging Mass Cytometry Reveals Tumor-Immune Microenvironment-Dependent Hormone Receptor Expression In Adult-Type Ovarian Granulosa Cell Tumors, Eleonora Y Khlebus, Veena K Vuttaradhi, Sammy Ferri-Borgogno, Allison L Brodsky, Barrett C Lawson, Samuel C Mok, R Tyler Hillman

Faculty, Staff and Student Publications

Adult-type granulosa cell tumors (AGCT) are rare ovarian tumors with few effective treatments for recurrent disease. To elucidate spatial features and cellular interactions within the AGCT tumor microenvironment, we applied imaging mass cytometry using a 34-marker panel on 130 regions from 24 AGCT samples, profiling more than 900,000 single cells. Analysis confirmed the immune “cold” phenotype of AGCTs and showed higher macrophage abundance in recurrent compared with primary tumors. We observed substantial heterogeneity in tissue architecture across samples, including variable presence of FOXL2+ cells embedded in collagen-rich regions (FOXL2+COL1A1+ cells). Based on tumor microenvironment composition, we defined two AGCT subtypes: …

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, Lucas Mccullum, Natalie A West, Clifton D Fuller, 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 …

Correction: Inflammation Mediated By Gut Microbiome Promotes Immune Suppression And Lung Adenocarcinoma Progression, Zahraa Rahal, Yuejiang Liu, Fuduan Peng, Sujuan Yang, Mohamed A Jamal, Manvi Sharma, Hannah Moreno, Ashish V Damania, 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, Damian L Stachura, Fátima Rivera-Escalera, David M Ruiz, 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.

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 …

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 …

Pka-Driven Spp1 Activation As A Novel Mechanism Connecting The Bone Microenvironment To Prostate Cancer Progression, Pablo Sanchis, Agustina Sabater, Julia Lechuga, Jimena Rada, Rocio Seniuk, Gaston Pascual, Mora Gatti, Juan Bizzotto, Peter D A Shepherd, Jun Yang, Javier Cotignola, Elba Vazquez, Joaquin Mateo, Pia Valacco, Estefania Labanca, Christopher Logothetis, Geraldine Gueron, Nicolas Anselmino

Faculty, Staff and Student Publications

Prostate cancer (PCa) bone metastasis (BM) poses a significant clinical challenge due to the heterogeneity of treatment responses and patient outcomes. In this study, we examined the role of Protein Kinase A (PKA) signaling in modulating the expression of osteopontin (SPP1/OPN), a protein associated with poor prognosis, within a subset of PCa BM patients. By integrating multi-omics results we identified a novel mechanism in which bone-derived type-I collagen (Col1a1) and fibronectin (Fn1) stimulate SPP1 expression in PCa cells through the activation of PKA signaling. This bone-induced regulation of SPP1 was confirmed both in vitro, using PCa-bone co-culture systems (PC3 or …

Childhood Trauma And Inflammatory Biomarker Effects On Cortical Thinning In Schizophrenia Spectrum Disorders, Samantha Narvaez, Yizhou Ma, Joshua Chiappelli, Hemalatha Sampath, Alia Warner, Peter Kochunov, Giselli Scaini, Anilkumar Pillai, 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 …

Dysregulated Sass6 Expression Promotes Increased Ciliogenesis And Cell Invasion Phenotypes, Eleanor Hargreaves, Rebecca Collinson, Andrew D Jenks, Adina Staszewski, Athanasios Tsalikis, Raquel Bodoque, Mar Arias-Garcia, Yasmin Abdi, Abdulaziz Al-Malki, Yinyin Yuan, Rachael Natrajan, Syed Haider, Thomas Iskratsch, Won-Jing Wang, Susana Godinho, Nicolaos J Palaskas, Fernando Calvo, Igor Vivanco, Tobias Zech, Barbara E Tanos

Faculty, Staff and Student Publications

Centriole and/or cilium defects are characteristic of cancer cells and have been linked to cancer cell invasion. However, the mechanistic bases of this regulation remain incompletely understood. Spindle assembly abnormal protein 6 homolog (SAS-6) is essential for centriole biogenesis and cilium formation. SAS-6 levels decrease at the end of mitosis and G1, resulting from APCCdh1-targeted degradation. To examine the biological consequences of unrestrained SAS-6 expression, we used a nondegradable SAS-6 mutant (SAS-6ND). This led to an increase in ciliation and cell invasion and caused an up-regulation of the YAP/TAZ pathway. SAS-6ND expression resulted in cell morphology changes, nuclear deformation, and …

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 …

Alterations In Region-Specific Gray Matter Volume Underlying Callous Unemotional Traits In Adolescents, Johannah Bashford-Largo, Ru Zhang, R James R Blair, Karina S Blair, Jaimie Elowsky, Matthew Dobbertin, Ahria J Dominguez, Melissa Hatch, Tyler Patrick, Sahil Bajaj

Faculty, Staff and Student Publications

Background: Callous-unemotional (CU) traits during adolescence, for example, shallow affect or lack of remorse, have been shown to be a risk marker for antisocial behavior. Only a few studies have investigated structural brain alterations underlying CU traits, and findings are inconclusive. The study examines CU symptomatology and gray matter volume (GMV) associations.

Methods: Structural brain MRI data were collected from a sample of 578 adolescents (60% male) with a mean age of 14.85 years (SD = 2.30; range = 10-19 years). CU traits were indexed via the Inventory for Callous Unemotional Traits (ICU). Region-wise volumetric parameters were obtained following parcellation …

Chromosome 20q Gene Signature Associated With Colorectal Cancer Progression, Jennifer Carter Jones, Apurva M Hegde, Yu-Jing Huang, Ganiraju Manyam, Vibhuti Srivastava, Jee Hoo Song, Yulan Cheng, Ralf Krahe, Warapen Treekitkarnmongkol, Stephen J Meltzer, Scott Kopetz, Stanley R Hamilton, Hiroshi Katayama, Subrata Sen

Faculty, Staff and Student Publications

Amplification of human chromosome 20q has been reported as the most frequently recurring genetic abnormality associated with large scale changes in mRNA and protein levels in sporadic colorectal carcinomas. While some studies have found 20q amplification to be consistent between primary and metastatic samples from the same patient with a role in the development of metastasis and worse patient prognosis, others have reported association with improved overall survival for a subset of these patients with colorectal cancer (CRC). To fine map the Minimal Common Regions (MCRs) of amplification on chromosome 20q and identify the candidate genes playing roles in progression …

Associations Of High Attenuation Area-Related Proteomic Biomarkers With Fibrotic Or Subpleural Interstitial Lung Abnormalities, John S Kim, Catherine L Debban, Daniel E Guzman, Riley T Hannan, Mary Salvatore, Claire Mcgroder, David Zhang, Anna J Podolanczuk, Daniel A Duprez, Shwu-Fan Ma, Yong Huang, Jeffrey M Sturek, Stephen S Rich, Jerome I Rotter, Rajat Deo, Ruth F Dubin, Janelle Vu Pugashetti, Jennifer M Wang, Meilan K Han, Justin M Oldham, Imre Noth, Prescott G Woodruff, Victor E Ortega, Julie C Fanburg-Smith, Edward B Stelow, Christopher A Moskaluk, Eric A Hoffman, Christine Kim Garcia, Russell P Bowler, Peter Ganz, R Graham Barr, Ani Manichaikul

Faculty, Staff and Student Publications

No abstract provided.

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, Victor Banerjee, Nicolas Mendez, Mohammad Shahnawaz, 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, Khushboo Irshad, Samer Sharafaldin, Nicole M Brossier, 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 …

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, Alejandra Serrano, Idania Lubo, Leticia Hamana, 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, Baljit S Khakh

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 …

Poziotinib For Egfr Exon 20-Insertion Nsclc: Clinical Efficacy Of The Phase 2 Zenith Trial And Differential Impact Of Egfr Exon 20 Insertion Location On Sensitivity, Xiuning Le, Jacqulyne P Robichaux, Monique Nilsson, R S K Vijayan, Ashwin Ravichandran, Jia Wu, Yasir Y Elamin, Lingzhi Hong, Jun Pei, Jun He, Sonia Patel, Hibiki Udagawa, Sriramvignesh Mani, Chang Woon Jang, Jeffrey M Clarke, Nishan Tchekmedyian, Jonathan W Goldman, Mark Socinski, Gajanan Bhat, Sharon Leu, Veronica Bunn, Zhenqiang Su, Sylvie Vincent, John W Lawson, Jason B Cross, John V Heymach

Faculty, Staff and Student Publications

EGFRex20 insertions (EGFRex20ins) can be classified as near- and far-loop based on the insertion location, however, the impact of location on responses to various EGFR tyrosine kinase inhibitors (TKIs) is poorly understood. In vitro studies show that afatinib, poziotinib, and zipalertinib more potently inhibited near-loop than far-loop insertions, whereas mobocertinib has similar IC50 in both groups. Molecular dynamics simulations reveal that near-loop insertions have multiple conformational states and lower transitional energy than far-loop insertions. ZENITH20 trial cohort 1 (NCT03318939) evaluates poziotinib in EGFRex20 NSCLC patients (n = 115) and demonstrates an objective response rate of 14.8% (95% Confidence …

Complete Genome Sequence Of Rothia Mucilaginosa D1, A Genetically Amenable Strain, Hemendra P. Dhaked, Isabella Andonie, Bo Yang, Vinayka M. Joshi, Zezhang T. Wen

School of Dentistry Faculty Publications

Here, we report the complete genome sequence of Rothia mucilaginosa D1. Unlike many other strains that have been sequenced, R. mucilaginosa D1, a clinical isolate, is genetically amenable. The complete sequencing of the genome provides potential for further studies on the genetics and pathophysiology of this emerging pathobiont.

Next-Gen Tools In Cancer Neuroscience, Vera Thiel, Debpali Sur, Caroline C Picoli, Tamara Mcerlain, Katalina Couto, David J Simon, Yuan Pan, Karen Olivia Dixon, Rajan P Kulkarni, Sebastien Talbot, Alexander Birbrair

Faculty, Staff and Student Publications

The emerging field of cancer neuroscience is rapidly evolving, driven by novel technologies and tools. These include advances in single-cell and spatial transcriptomics; genetic mouse models paired with automated high-throughput; and innovative optical electrophysiological approaches, optogenetics, chemogenetics, engineered viruses, and new methods for visualizing neuronal activity. Collectively, these technologies are revolutionizing how we investigate, manipulate, and characterize distinct components that contribute to the nervous system-cancer interface. In the present review, we discuss the key technologies that are closing the gap between oncology and neuroscience, highlighting the innovations that are propelling the cancer neuroscience field forward.

Rna/Dna-Binding Protein Tdp43 Regulates Dna Mismatch Repair Genes With Implications For Genome Stability, Vincent E Provasek, Albino Bacolla, Suganya Rangaswamy, Manohar Kodavati, Joy Mitra, Issa O Yusuf, Vikas H Malojirao, Velmarini Vasquez, Gavin W Britz, Guo-Min Li, Zuoshang Xu, Sankar Mitra, Ralph M Garruto, John A Tainer, Muralidhar L Hegde

Faculty, Staff and Student Publications

TDP43 is an RNA/DNA-binding protein increasingly recognized for its role in neurodegenerative conditions, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). As characterized by its aberrant nuclear export and cytoplasmic aggregation, TDP43 proteinopathy is a hallmark feature in over 95% of ALS/FTD cases, leading to detrimental cytosolic aggregates and a reduction in nuclear functionality in neurons. Building on our prior work linking TDP43 proteinopathy to the accumulation of DNA double-strand breaks (DSBs) in neurons, the present investigation uncovers a novel regulatory relationship between TDP43 and DNA mismatch repair (MMR) gene expression. Here, we show that TDP43 depletion or overexpression …