Digital Commons Network^™

Lifelong Aortic Risk In Turner Syndrome: Unexpected Aortic Events In Asymptomatic Patients, Milan Jaiswal, Sara Mansoorshahi, Sharon Zachariah, Thanila Macedo, Alana C Cecchi, Akiko Tanaka, Anthony L Estrera, Rana O Afifi, Gustavo S Oderich, Dianna M Milewicz, Siddharth K Prakash

Faculty, Staff and Student Publications

Individuals with Turner syndrome (TS) face a high relative risk of acute aortic dissection compared with the general population. Dissection risk is greatest in those who have congenital heart disease, thoracic aortic aneurysms, or hypertension. This case report features two adult patients with TS who presented with asymptomatic thoracic aortic pathologies that were identified on routine surveillance imaging. Both patients were active and denied cardiovascular symptoms, even as they developed high-risk aortic lesions that evolved rapidly on initial serial images. These two cases illustrate how lifelong cardiovascular surveillance of TS patients can save lives.

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, G Elisabeta Marai, 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 …

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, Helen Clark, Bryan Fellman, Ying Yuan, 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: …

Understanding Infectious Complications In Patients With Lower-Risk Myelodysplastic Syndromes: A Step Towards Improving Survival, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

No abstract provided.

Transfer Learning Via Distributed Brain Recordings Enables Reliable Speech Decoding, Aditya Singh, Tessy Thomas, Jinlong Li, Greg Hickok, Xaq Pitkow, Nitin Tandon

Faculty, Staff and Student Publications

Speech brain-computer interfaces (BCIs) combine neural recordings with large language models to achieve real-time intelligible speech. However, these decoders rely on dense, intact cortical coverage and are challenging to scale across individuals with heterogeneous brain organization. To derive scalable transfer learning strategies for neural speech decoding, we used minimally invasive stereo-electroencephalography recordings in a large cohort performing a demanding speech motor task. A sequence-to-sequence model enabled decoding of variable-length phonemic sequences prior to and during articulation. This enabled development of a cross-subject transfer learning framework to isolate shared latent manifolds while enabling individual model initialization. The group-derived decoder significantly outperformed …

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, Izuma Nakayama, Christos Fountzilas, Dani R Castillo, 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 …

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 …

Ethical Sourcing In The Context Of Health Data Supply Chain Management: A Value Sensitive Design Approach, Camille Nebeker, Jean Christophe Bélisle-Pipon, Benjamin X Collins, Ashley Cordes, Kadija Ferryman, Brian J Mcinnis, Shannon K Mcweeney, Laurie L Novak, Susannah Rose, Joseph M Yracheta, Ishan C Williams, Xiaoqian Jiang, Ellen W Clayton, Bradley A Malin, Bridge2ai Ethical, Legal And Social Implications Ai Working Group

Faculty, Staff and Student Publications

Objective: The Bridge2AI program is establishing rules of practice for creating ethically sourced health data repositories to support the effective use of ML/AI in biomedical and behavioral research. Given the initially undefined nature of ethically sourced data, this work concurrently developed definitions and guidelines alongside repository creation, grounded in a practical, operational framework.

Materials and methods: A Value Sensitive Design (VSD) approach was used to explore ethical tensions across stages of health data repository development. The conceptual investigation drew from supply chain management (SCM) processes to (1) identify actors who would interact with or be affected by the data repository …

Factors Associated With Medication Adherence Among Patients With Attention-Deficit/Hyperactivity Disorder (Adhd), Linh Nguyen, Yen-Chi L Le, Hannah Reygaerts, Todd R Johnson, Cesar A Soutullo

Faculty, Staff and Student Publications

Objective: Attention-Deficit/Hyperactivity Disorder (ADHD) is a common behavioral health condition that impacts 5% to 8% of children and 2.5% of adults worldwide. The symptoms of ADHD are effectively managed with medication, yet patients with ADHD may inconsistently take their medication. We assessed medication adherence among patients with ADHD and identified factors associated with medication adherence that may be utilized to optimize adherence.

Method: This is a retrospective, observational study among patients aged 4 years and older with a diagnosis of ADHD at primary care and multispecialty outpatient clinics during May 2021 to May 2023. We assessed sociodemographic characteristics, stratified by …

Ethical Sourcing In The Context Of Health Data Supply Chain Management: A Value Sensitive Design Approach, Camille Nebeker, Jean Christophe Bélisle-Pipon, Benjamin X Collins, Ashley Cordes, Kadija Ferryman, Brian J Mcinnis, Shannon K Mcweeney, Laurie L Novak, Susannah Rose, Joseph M Yracheta, Ishan C Williams, Xiaoqian Jiang, Ellen W Clayton, Bradley A Malin, Bridge2ai Ethical, Legal And Social Implications Ai Working Group

Faculty, Staff and Student Publications

Objective: The Bridge2AI program is establishing rules of practice for creating ethically sourced health data repositories to support the effective use of ML/AI in biomedical and behavioral research. Given the initially undefined nature of ethically sourced data, this work concurrently developed definitions and guidelines alongside repository creation, grounded in a practical, operational framework.

Materials and methods: A Value Sensitive Design (VSD) approach was used to explore ethical tensions across stages of health data repository development. The conceptual investigation drew from supply chain management (SCM) processes to (1) identify actors who would interact with or be affected by the data repository …

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.

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 …

Liver-Specific Expression Of Hiv-1 Viral Protein R Causes Hepatic Steatosis And Glucose Intolerance In Male Mice, Neeti Agarwal, Pradip Saha, Claudia E Ramirez Bustamante, Sean M Hartig, Mark A Herman, Ashok Balasubramanyam, Jordan E Lake

Faculty, Staff and Students Publications

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized in people with HIV (PWH), with both HIV and antiretroviral therapy contributing to liver damage and glucose intolerance. However, the role of viral proteins derived from reservoirs in this process remains unclear.

Methods: Adeno-associated virus (AAV) constructs encoding a control protein or HIV-1 viral protein R (Vpr) driven by the thyroxine-binding globulin promoter were administered to male mice (n = 5 per group) fed regular chow or a high-fat diet (HFD). Young adult mice underwent intraperitoneal glucose tolerance testing and magnetic resonance imaging, followed by euthanasia. Liver and adipose tissues …

Item Selection For The Development And Validation Of A Revised Classification Criteria For Adult And Juvenile Idiopathic Inflammatory Myopathies: Myoroc Project, Didem Saygin, Rachel Zeng, Stefanie Glaubitz, Matteo Bottai, Anthony A Amato, Lorenzo Cavagna, Sonye K Danoff, Marianne De Visser, Mazen M Dimachkie, Manabu Fujimoto, Masataka Kuwana, Pedro M Machado, Merrilee Needham, Clarissa Pilkington, Liza Rajasekhar, Lisa G Rider, Yasser Salem, Samuel Katsuyuki Shinjo, Jasvinder A Singh, Mohammed Tikly, Guochun Wang, Victoria P Werth, Rohit Aggarwal, Ingrid E Lundberg

Faculty, Staff and Students Publications

Objective: A revision of the 2017 EULAR-ACR myositis classification criteria, namely EULAR-ACR funded Myositis Revision of Classification (MyoROC) project, is currently underway involving a large international group of experts. In the first phase of this project, we identified additional items to be tested in the criteria.

Methods: We distributed an electronic survey to International Myositis Assessment and Clinical Studies (IMACS) members to identify new items. The identified items were discussed within the Steering Committee and a multi-step Delphi consensus process consisting of an open discussion and three rounds of e-voting were conducted to reach the final item list.

Results: The …

Inhibition Of Ros1 Activity With Lorlatinib Reversibly Suppresses Fertility In Male Mice, Yuki Oyama, Kentaro Shimada, Haruhiko Miyata, Rie Iida-Norita, Chihiro Emori, Maki Kamoshita, Seiya Oura, Ryohei Katayama, Martin M Matzuk, Masahito Ikawa

Faculty, Staff and Students Publications

Background: Inhibition of sperm maturation in the epididymis is a promising post-testicular strategy for short-acting male contraceptives. It has been shown that ROS1, a receptor tyrosine kinase expressed in the epididymis, is essential for epididymal differentiation, sperm maturation, and male fertility in mice. However, it is unknown if inhibition of ROS1 suppresses male fertility reversibly.

Objectives: Our study aimed to investigate the effects of ROS1 inhibitor administration in male mice on sperm function and fertility.

Materials and methods: We used lorlatinib, an anti-cancer drug that inhibits ROS1. We treated 10-week-old sexually mature male mice with lorlatinib for 3 weeks and …

Endoglin-Directed Car T Cells Comprehensively Target Tumors In Advanced Sarcomas, Harrison R Berger, Malina Maharana, Jeneffer Mirabal, Lyazat Kurenbekova, Alberto Delaidelli, Atreyi Dasgupta, Ahmed Z Gad, Mohamed F Sheha, Sybrina S Kerr, Ada I Ozcan, Jessica S Morris, Angela M Major, M John Hicks, Mary K Mckenna, Ben K Seon, Matthew L Baker, Poul H Sorensen, Meenakshi Hegde, Jason T Yustein, Nabil Ahmed, Sujith K Joseph

Faculty, Staff and Students Publications

There are limited therapeutic options for patients with advanced sarcomas, which leads to dismal outcomes for children and adults. Although chimeric antigen receptor (CAR) T cells hold promise for treating advanced sarcomas, this approach is constrained by a paucity of effective targets. Our previous clinical study identified endoglin (ENG/CD105), a TGFβ coreceptor, as a target of the endogenous immune response in a patient with sarcoma who exhibited an exceptional response to HER2-targeted CAR T-cell therapy. ENG is expressed on various sarcomas, cancer-associated fibroblasts, and neoangiogenic vessels and therefore offers comprehensive tumor targeting. Furthermore, ENG knockout in sarcoma cells reduces their …

Phosphorylation At Serine 214 Correlates With Tau Seeding Activity In An Age-Dependent Manner In Two Mouse Models For Tauopathies And Is Required For Tau Transsynaptic Propagation, Pablo Martinez, Nur Jury-Garfe, Henika Patel, Yanwen You, Abigail Perkins, Yingjian You, Audrey Lee-Gosselin, Ruben Vidal, Cristian A Lasagna-Reeves

Faculty, Staff and Students Publications

Background

Tau aggregation and propagation are hallmark features of Alzheimer's disease and related tauopathies. The molecular identity and post-translational modifications that contribute to tau seeding activity remain incompletely understood.

Objective

To characterize the temporal dynamics of tau seeding activity and identify specific phosphorylated tau species associated with tau propagation in vivo.

Methods

We profiled tau seeding activity using a FRET-based biosensor cell line and correlated it with the abundance of phospho- and conformational tau species in two transgenic mouse models of tauopathy (P301S-1N4R and P301S-0N4R). Immunohistochemistry and subcellular fractionation were used to examine the spatial distribution of tau species. Functional …

Systematic Targeting Of Gd2-Positive Neuroblastoma Tumors With A Photooncolytic Phage Nanovector Platform, Suleman Khan Zadran, Nicola Facchinello, Piergiuseppe De Rosa, Roberto Saporetti, Paolo Emidio Costantini, Luca Ulfo, Michela Nigro, Annapaola Petrosino, Lucia Pappagallo, Sara Aloisi, Giorgio Milazzo, Zainul Abe Din, Alberto Rigamonti, Leonardo Flora, Martina Santulli, Leonardo Cimadom, Giampaolo Zuccheri, Mattia Zangoli, Manuele Di Sante, Matteo Di Giosia, Francesca Di Maria, Roberto Bernardoni, Eveline Barbieri, Matteo Calvaresi, Alberto Danielli, Giovanni Perini

Faculty, Staff and Students Publications

Disialoganglioside-GD2 is a key molecular target for Neuroblastoma (NB) immunotherapy based on the employment of GD2-targeting antibodies. However, about 50% of treated patients can experience tumor relapse due to limited immune-mediated cytotoxicity and poor antibody penetration into tumors. To address this problem, a tumor-penetrating photo-oncolytic phage nanovector platform is genetically and chemically developed that selectively targets GD2-expressing NB cells. The phage bioconjugates, functionalized with different photosensitizers, result in specific and selective oncolysis of GD2-positive NB cells upon light irradiation, without affecting GD2-negative ones. The photo-oncolytic phage vectors are shown to deeply penetrate into GD2-positive tumor spheroids in vitro, and to …

Does Every Person With Asthma Need An Inhaled Corticosteroid?, Harold J Farber

Faculty, Staff and Students Publications

No abstract provided.

Molecular And Genetic Landscapes Of Retina And Brain Microglia In Neurodegenerative Diseases, Khang Ma, Rinki Ratnapriya

Faculty, Staff and Students Publications

Microglia-driven dysregulation has emerged as a significant underlying mechanism in many neurodegenerative diseases, such as age-related macular degeneration (AMD) and Alzheimer's disease (AD). Although both brain and retinal microglia originate from the yolk sac, it is uncertain whether they share molecular similarities or genetic and molecular foundations related to neurodegenerative diseases. In this study, we examine the transcriptomic and epigenetic profiles of retina and brain microglia through integrative analyses of single-nucleus RNA sequencing (snRNA-seq) and single-nucleus ATAC sequencing (snATAC-seq) from 97 independent human samples across 11 different studies. Our findings reveal that retina and brain microglia share similar expression and …