Digital Commons Network^™

Ppp2r1a Mutations Portend Improved Survival After Cancer Immunotherapy, Yibo Dai, Anne Knisely, Mitsutake Yano, Minghao Dang, Emily M Hinchcliff, Sanghoon Lee, Annalyn Welp, Manoj Chelvanambi, Matthew Lastrapes, Heng Liu, Zhe Yuan, Chen Wang, Hao Nie, Stephanie Jean, Luis J Montaner, Jiakai Hou, Ami Patel, Shrina Patel, Bryan Fellman, Ying Yuan, Baohua Sun, Renganayaki Krishna Pandurengan, Edwin Roger Parra Cuentas, Joseph Celestino, Yan Liu, Jinsong Liu, R Tyler Hillman, Shannon N Westin, Anil K Sood, Pamela T Soliman, Aaron Shafer, Larissa A Meyer, David M Gershenson, David Vining, Dhakshinamoorthy Ganeshan, Karen Lu, Jennifer A Wargo, Weiyi Peng, Rugang Zhang, Linghua Wang, Amir A Jazaeri

Faculty, Staff and Student Publications

Immune checkpoint blockade (ICB) therapy is effective against many cancers, although resistance remains a major issue and new strategies are needed to improve clinical outcomes1-5. Here we studied ICB response in a cohort of patients with ovarian clear cell carcinoma-a cancer type that poses considerable clinical challenges and lacks effective therapies6-8. We observed significantly prolonged overall survival and progression-free survival in patients with tumours with PPP2R1A mutations. Importantly, our findings were validated in additional ICB-treated patient cohorts across multiple cancer types. Translational analyses from tumour biopsies demonstrated enhanced IFNγ signalling, and the presence of tertiary lymphoid structures at the baseline, …

Large-Scale Genome-Wide Analyses Of Stuttering, Hannah G Polikowsky, Alyssa C Scartozzi, Douglas M Shaw, Dillon G Pruett, Hung-Hsin Chen, Lauren E Petty, Alexander S Petty, Emily J Lowther, Shu-Hsien Cho, Yao Yu, Sahar Mozaffari, Christy L Avery, Kathleen Mullan Harris, Reyna L Gordon, Janet M Beilby, Kathryn Z Viljoen, Robin M Jones, Chad D Huff, Heather M Highland, Shelly Jo Kraft, Jennifer E Below

Faculty, Staff and Student Publications

Developmental stuttering is a highly heritable, common speech condition characterized by prolongations, blocks and repetitions of speech. Although stuttering is highly heritable and enriched within families, the genetic architecture is largely understudied. We reasoned that there are both shared and distinct genetic variants impacting stuttering risk within sex and ancestry groups. To test this idea, we performed eight primary genome-wide association analyses of self-reported stuttering that were stratified by sex and ancestry, as well as secondary meta-analyses of more than one million individuals (99,776 cases and 1,023,243 controls), identifying 57 unique loci. We validated the genetic risk of self-reported stuttering …

Bard: A Seamless Two-Stage Dose Optimization Design Integrating Backfill And Adaptive Randomization, Yixuan Zhao, Rachael Liu, Jianchang Lin, Ying Yuan

Faculty, Staff and Student Publications

One common approach for dose optimization is a two-stage design, which initially conducts dose escalation to identify the maximum tolerated dose, followed by a randomization stage where patients are assigned to two or more doses to further assess and compare their risk-benefit profiles to identify the optimal dose. A limitation of this approach is its requirement for a relatively large sample size. To address this challenge, we propose a seamless two-stage design, BARD (Backfill and Adaptive Randomization for Dose Optimization), which incorporates two key features to reduce sample size and shorten trial duration. The first feature is the integration of …

High-Gamma And Beta Bursts In The Left Supramarginal Gyrus Can Differentiate Verbal Memory States And Performance, Shennan Aibel Weiss, Nicolás Sawczuk, Daniel Y. Rubinstein, Michael R Sperling, Katrina Wendel-Mitoraj, Päivi Österman, René Dumay-Roscher, Charles B. Mikell, Sima Mofakham, Kelly Coulehan, Petar M. Djuric, Diego Fernandez Slezak, Juan Esteban Kamienkowski

Department of Neurology Faculty Papers

INTRODUCTION: The left supramarginal gyrus (LSMG) contributes to attentional allocation for memory encoding and may also reflect memory state and performance. Given the roles of high-gamma and beta bursts in cognition and memory, this proof-of-concept study investigated whether these signals within the LSMG could classify memory state and performance.

METHODS: Using secondary data from 103 epilepsy patients undergoing presurgical iEEG evaluation, we analyzed 141 delayed verbal free recall experiments. Intracranial EEG (iEEG) data, recorded solely from LSMG electrode contacts, were processed to create two-dimensional (2D) tensors of convolved high-gamma (HG), and beta (15-40 Hz) burst activity. Convolutional neural networks (CNNs) …

The Eleventh Annual Meeting Of The Southeastern Association Of Shared Resources (Seasr) Nashville, Tn, Usa June 12-14, 2024, Jenny C Schafer, Lyra M Griffiths, Tania E Mesa, Deidre Daria, Daniel Kraushaar, Kristen V Massey, Edith M Sampson, Laura Fox-Goharioon, Laxminarayanan Krishnan, Stacie Woolard, Aaron Pitre

Faculty, Staff and Students Publications

No abstract provided.

Single-Cell Transcriptomics Reveals Biomarker Heterogeneity Linked To Cdk4/6 Inhibitor Resistance In Breast Cancer Cell Lines, Ilenia Migliaccio, Martina Bonechi, Dario Romagnoli, Giulia Boccalini, Francesca Galardi, Cristina Guarducci, Agostina Nardone, Rachel Schiff, Laura Biganzoli, Luca Malorni, Matteo Benelli

Faculty, Staff and Students Publications

Cyclin dependent kinases 4 and 6 inhibitors have brought great improvements in the treatment of luminal breast cancer, but resistance is a major clinical hurdle. Multiple biomarkers of resistance have been proposed, but none is currently utilized in clinical practice. By performing single-cell RNA sequencing of seven palbociclib-naïve luminal breast cancer cell lines and palbociclib-resistant derivatives, we show that established biomarkers and pathways related to CDK4/6i resistance present marked intra- and inter- cell-line heterogeneity. Transcriptional features of resistance could be already observed in naïve cells correlating with levels of sensitivity (IC50) to palbociclib. Resistant derivatives showed transcriptional clusters that significantly …

Role And Use Of Race In Artificial Intelligence And Machine Learning Models Related To Health, Martin C Were, Ang Li, Bradley A Malin, Zhijun Yin, Joseph R Coco, Benjamin X Collins, Ellen Wright Clayton, Laurie L Novak, Rachele Hendricks-Sturrup, Abiodun O Oluyomi, Shilo Anders, Chao Yan

Faculty, Staff and Students Publications

The role and use of race within health-related artificial intelligence (AI) and machine learning (ML) models have sparked increasing attention and controversy. Despite the complexity and breadth of related issues, a robust and holistic framework to guide stakeholders in their examination and resolution remains lacking. This perspective provides a broad-based, systematic, and crosscutting landscape analysis of race-related challenges, structured around the AI and ML life cycle and framed through "points to consider" to support inquiry and decision-making.

Dosimetric Comparisons Of 6mv, 6fff, 10mv, And 10fff On Vmat Planning In Patients With Endometrial Cancer, Madisin M. Depas

Masters Projects

Purpose: This study aimed to evaluate the dosimetric and efficiency impacts of different photon beam energies—6MV, 6 flattening filter free (FFF), 10MV, and 10FFF—on volumetric modulated arc therapy (VMAT) plans for endometrial cancer, with attention to target coverage, organ at risk (OAR) sparing, and treatment efficiency.

Methods: A retrospective analysis was conducted on 25 patients with post-hysterectomy endometrial cancer. Each patient received four VMAT plans with varying energies. Planning metrics assessed included planning target volume (PTV) dose maximum (Dmax), conformity index (CI), heterogeneity index (HI), OAR doses (bladder, bowel, rectum), and total monitor units (MU). Correlations were drawn …

Structural Variants: Mechanisms, Mapping, And Interpretation In Human Genetics, Shruti Pande, Moez Dawood, Christopher M Grochowski

Faculty, Staff and Students Publications

Structural variations (SVs) represent genomic variations that involve breakage and rejoining of DNA segments. SVs can alter normal gene dosage, lead to rearrangements of genes and regulatory elements within a topologically associated domain, and potentially contribute to physical traits, genomic disorders, or complex traits. Recent advances in sequencing technologies and bioinformatics have greatly improved SV detection and interpretation at unprecedented resolution and scale. Despite these advances, the functional impact of SVs, the underlying SV mechanism(s) contributing to complex traits, and the technical challenges associated with SV detection and annotation remain active areas of research. This review aims to provide an …

Xpert Mtb/Rif Ultra Assay For Pulmonary Tuberculosis And Rifampicin Resistance In Adults And Adolescents, David J Horne, Jerry S Zifodya, Adrienne E Shapiro, Elizabeth Chandler Church, Jonah S Kreniske, Alexander W Kay, Katie Scandrett, Karen R Steingart, Yemisi Takwoingi

Faculty, Staff and Students Publications

Background: Xpert MTB/RIF Ultra (Xpert Ultra) is a molecular World Health Organization (WHO)-recommended rapid diagnostic test that simultaneously detects tuberculosis and rifampicin resistance. This review updates a comparative accuracy Cochrane review of Xpert MTB/RIF and Xpert Ultra as Xpert Ultra has replaced Xpert MTB/RIF.

Objectives: To determine the diagnostic accuracy of Xpert MTB/RIF Ultra (Xpert Ultra) for detecting pulmonary tuberculosis and rifampicin resistance in adults and adolescents with presumptive tuberculosis based on signs or symptoms or with an abnormal chest x-ray suggestive of tuberculosis.

Search methods: We searched seven databases including CENTRAL, MEDLINE, and Embase, plus two trial registers (ClinicalTrials.gov …

Lessons In Longevity From Blood Stem Cells Under Protein Stress, André Catic

Center on Aging Staff Publications

Blood stem cells are among the body's longest-living cells despite being highly vulnerable to proteotoxic damage, which accelerates their aging. To maintain protein homeostasis (proteostasis), hematopoietic stem cells (HSCs) employ mechanisms such as reduced translation rates, high chaperone activity, autophagy, and selective protein degradation. These strategies mitigate protein misfolding, maintain quiescence, and preserve regenerative potential. Disruptions in proteostasis can lead to the elimination of impaired HSCs through differentiation or apoptosis, ensuring the integrity of the stem cell pool. Due to the systemic impact of the blood on aging and its experimental and clinical accessibility, investigating HSC proteostasis provides insights into …

A Phase I Trial Of Evorpacept, Lenalidomide And Rituximab For Patients With B-Cell Non-Hodgkin Lymphoma, Paolo Strati, Lei Feng, Andrey Tyshevich, Darya Shavronskaya, Julia Alesse, Noel English, Elizabeth Sheehan, Nikita Syzrantsev, Alexander Nesmelov, Tony Z Zhuang, Dai Chihara, Jason R Westin, Sairah Ahmed, Luis E Fayad, Jared Henderson, Kylie Dent, Elizabeth Mcchesney, Sattva S Neelapu, Christopher R Flowers

Faculty, Staff and Student Publications

Introduction: SIRPα+ macrophages can mediate resistance to lenalidomide and rituximab (R2) in patients with B-cell non-Hodgkin lymphoma (B-NHL). Evorpacept (ALX148) is a novel CD47 blocker that abrogates interactions between lymphoma cells and SIRPα+ macrophages.

Methods: Adult patients with B-NHL who had received at least 2 prior lines of systemic therapy were included in this single arm phase I study (NCT05025800). Evorpacept was administered intravenously (IV), in a 28-day cycle, until progression, at two dose levels (DL): 30 mg/Kg on day (D) 1 and D15 (DL1), or 60 mg/Kg on day 1 (DL2); rituximab 375 mg/m2 IV was given …

Epigenomic Diagnosis And Prognosis Of Acute Myeloid Leukemia., Francisco Marchi, Vivek M. Shastri, Richard J. Marrero, Nam H K Nguyen, Antonella Öttl, Ann-Kathrin Schade, Marieke Landwehr, Olga Krali, Jessica Nordlund, Matin Ghavami, Fernando Sckaff, Vikash K. Mansinghka, Xueyuan Cao, William Slayton, Petr Starostik, Christopher R. Cogle, Raul C. Ribeiro, Jeffrey E. Rubnitz, Jeffery Klco, Abdelrahman Elsayed, Alan S. Gamis, Timothy J. Triche, Rhonda Ries, E Anders Kolb, Richard Aplenc, Todd Alonzo, Stanley Pounds, Soheil Meshinchi, Jatinder K. Lamba

Manuscripts, Articles, Book Chapters and Other Papers

Despite the critical role of DNA methylation, clinical implementations harnessing its promise have not been described in acute myeloid leukemia. Utilizing DNA methylation from 3314 leukemia patient samples across 11 harmonized cohorts, we describe the Acute Leukemia Methylome Atlas, which includes robust models capable of accurately predicting AML subtypes. A genome-wide prognostic model as well as a targeted panel of 38 CpGs significantly predict five-year survival in our pediatric and adult test cohorts. To accelerate rapid clinical utility, we develop a specimen-to-result protocol that uses long-read nanopore sequencing and machine learning to characterize patients' whole genomes and epigenomes. Clinical validation …

Superficial Cervical Plexus Block For Postoperative Pain Management In Occipital Craniotomies: A Narrative Review, Shahab Ahmadzadeh, Bennett M. Ford, Alex V. Hollander, Mary Kathleen Luetkemeier, Tomasina Q. Parker-Actlis, Sahar Shekoohi

School of Medicine Faculty Publications

Post-craniotomy pain is common yet often sub-optimally managed because systemic opioids can obscure postoperative neurologic examinations. The superficial cervical plexus block (SCPB) has, therefore, emerged as a targeted regional anesthesia option for occipital craniotomies. The SCPB targets the C2-C4 nerves to anesthetize the occipital scalp region, covering the lesser occipital nerve territory that lies within typical posterior scalp incisions. Clinical evidence shows the block is effective in reducing acute postoperative pain after occipital craniotomy and diminishes opioid requirements. Studies have demonstrated successful and long-lasting analgesia, reductions in 24-h opioid consumption, and a lower incidence of severe pain. Moreover, the technique …

Phosphoglycerate Mutase Regulates Treg Differentiation Through Control Of Serine Synthesis And One-Carbon Metabolism, Wesley H Godfrey, Judy J Lee, Shruthi Shanmukha, Kaho Cho, Xiaojing Deng, Chandra Shekar R Ambati, Vasanta Putluri, Abu Hena Mostafa Kamal, Paul M Kim, Nagireddy Putluri, Michael D Kornberg

Faculty, Staff and Students Publications

The differentiation and suppressive functions of regulatory CD4 T cells (Tregs) are supported by a broad array of metabolic changes, providing potential therapeutic targets for immune modulation. In this study, we focused on the regulatory role of glycolytic enzymes in Tregs and identified phosphoglycerate mutase (PGAM) as being differentially overexpressed in Tregs and associated with a highly suppressive phenotype. Pharmacologic or genetic inhibition of PGAM reduced Treg differentiation and suppressive function while reciprocally inducing markers of a pro-inflammatory, T helper 17 (Th17)-like state. The regulatory role of PGAM was dependent on the contribution of 3-phosphoglycerate (3 PG), the PGAM substrate, …

A Novel Microdosimetry-Based Formalism For Cell Survival Modelling Applicable To Hypofractionated Radiotherapy, Oleg N Vassiliev, Radhe Mohan

Faculty, Staff and Student Publications

Objectives

Hypofractionated radiotherapy requires reliable cell survival models for doses much higher than the standard 2 Gy, for which the linear-quadratic (LQ) model is not applicable. We developed an alternative approach applicable to both low doses and high doses used in hypofractionated treatments and radiobiological experiments.

Approach.

We combined a standard microdosimetric technique with a recently introduced non-LQ cell survival model. Our formulation accounts for cell damage by multi-track events involving any number of particles. This is necessary for modelling cell survival at therapeutic doses. We characterise each cell type by the size �� of the sensitive volume (SV) and …

Comparison Of Recurrence Rates In Chemical Matricectomy With Phenol And Nail Bracing: A Scoping Review, Jessica Sima, Amanda Killeen

School of Podiatric Medicine - Student Research

Introduction: Ingrown toenails are one of the most common nail conditions and are usually treated with chemical matricectomy using phenol (CMP). However, this procedure is often contraindicated in patients with diabetes mellitus or peripheral vascular disease. Orthonyxia, or nail braces application, is a non-invasive alternative treatment for ingrown toenails. The nail braces are spring wires with one side shaped into a hook that is placed under one side of the nail, and the other side attached to a plastic pad that is glued to the nail plate. The braces retain the normal shape of the nails without removing them, allowing …

Impact Of Prostate Volume On Dose Fall-Off And Organ-At-Risk Exposure In Vmat For Prostate Cancer, Zhikang Jiang

Masters Projects

Prostate cancer remains one of the most prevalent malignancies among men, with radiotherapy, particularly VMAT—playing a central role in its management. VMAT allows for highly conformal dose delivery, but treatment planning must strike a careful balance between achieving steep dose gradients around the prostate and minimizing radiation exposure to nearby organs at risk (OARs), such as the bladder and rectum. This study aimed to evaluate how prostate volume influences dose fall-off characteristics and OAR dose exposure in VMAT treatment plans, providing insights into optimizing radiotherapy for patients with varying prostate sizes. A retrospective analysis was conducted on 50 prostate cancer …

Assessment Of Dnase Activity By Ratiometric Fluorescence Resonance Energy Transfer, Candace L Minchew, Vladimir V Didenko

Faculty, Staff and Students Publications

The present protocol describes a simple and sensitive ratiometric Förster resonance energy transfer (FRET) assay for the detection and quantitative assessment of DNase activity. Ratiometric FRET measurements make use of the ratio of donor and acceptor emission signals. The assay detects single-stranded DNA breaks using a staple-shaped, dual-tagged 38-mer FRET oligoprobe, employed as a real-time DNA cleavage sensor. The main application of the described approach is the quantitative assessment of the effects of reaction conditions, such as pH, temperature, and buffer composition, on DNase activity. Due to its ability to detect even minor and slow DNA cleavage, the assay is …

Human Ipsc-Based Breast Cancer Model Identifies S100p-Dependent Cancer Stemness Induced By Brca1 Mutation, Jingxin Liu, Cai Zhao, Jiahao Chen, Pengguihang Zeng, Qingjian Li, Ranran Dai, Xingqiang Lai, Wenqian Song, Jianing Chen, Xixi Zhu, Xinyi Liu, Jun Sun, Jia Wang, Peihang Fang, Tengfei Wang, Wenjie Chen, Diana Guallar, Nan Cao, Jianli Zhao, Shicheng Su, Andy Peng Xiang, Yi Arial Zeng, Jie Li, Junchao Cai, Dung-Fang Lee, Jinxin Bei, Yongliang Huo, Hai Hu, Shengbao Suo, Dong-Feng Huang, Jin Bai, Junjun Ding

Faculty, Staff and Student Publications

Breast cancer is the most common malignancy in females and remains the leading cause of cancer-related deaths for women worldwide. The cellular and molecular basis of breast tumorigenesis is not completely understood partly due to the lack of human research models which simulate the development of breast cancer. Here, we developed a method for generating functional mammary-like cells (MCs) from human-induced pluripotent stem cells (iPSCs). The iPSC-MCs closely resemble human primary MCs at cellular, transcriptional, and functional levels. Using this method, a breast cancer model was generated using patient-derived iPSCs harboring germline

The Sodium-Glutamate Antagonist Riluzole Improves Outcome After Acute Spinal Cord Injury: Results From The Riscis Randomised Controlled Trial Analysed Using A Global Statistical Analytic Technique, Michael G. Fehlings, Karlo M. Pedro, Mohammed Ali Alvi, Ali Moghaddamjou, James S. Harrop, Ralph Stanford, Jonathon Ball, Bizhan Aarabi, Paul M. Arnold, James D. Guest, Shekar N. Kurpad, James M. Schuster, Ahmad N. Nassr, Karl M. Schmitt, Jefferson R. Wilson, Darrel S. Brodke, Faiz U. Ahmad, Albert Yee, Wilson Z. Ray, Nathaniel P. Brooks, Jason Wilson, Diana S-L Chow, Elizabeth G. Toups, Kevin E. Thorpe, Jiaxin Huang, Peng Huang

Department of Neurosurgery Faculty Papers

BACKGROUND: Spinal cord injury (SCI) clinical trials typically rely on a single primary endpoint to assess drug efficacy. This strategy fails to adequately capture the full impact of treatment in heterogenous neurological conditions like SCI. A more patient-centric analysis requires assessment of neurological function, functional capacity, and quality of life, incorporating meaningful patient-reported outcomes. The global statistical test (GST) addresses this challenge using a unified statistical conclusion regarding the superiority of a treatment strategy over another by evaluating multiple trial endpoints simultaneously.

METHODS: The RISCIS trial (Safety and Efficacy of Riluzole in Acute Spinal Cord Injury Study) data was analysed …

Anxious Traits Intensify The Impact Of Depressive Symptoms On Stigma In People Living With Hiv, Alexia Koukopoulos, Antonio Maria D'Onofrio, Alessio Simonetti, Delfina Janiri, Flavio Cherubini, Paolo Vassalini, Letizia Santinelli, Gabriella D'Ettorre, Gabriele Sani, Giovanni Camardese

Faculty, Staff and Students Publications

Background/Objectives: Despite medical advances, stigma remains a major challenge for people living with HIV (PLWH). This study examined clinical, sociodemographic, and psychological predictors of HIV-related stigma, and explored whether affective temperament moderates the impact of depression on stigma.

Methods: This cross-sectional observational study included 97 PLWH attending a tertiary infectious disease unit in Rome, Italy. Participants completed a battery of validated psychometric instruments assessing depressive symptoms, anxiety, manic symptoms, mixed affective states, general psychopathology, impulsivity, and affective temperament. HIV-related stigma was evaluated using the Berger HIV Stigma Scale, which measures personalized stigma, disclosure concerns, negative self-image, and concerns …

Minimal Ablative Margin Quantification Using Hepatic Arterial Versus Portal Venous Phase Ct For Colorectal Metastases Segmentation: A Dual-Center, Retrospective Analysis, Noreen S Siddiqi, Yuan-Mao Lin, Jessica Albuquerque Marques Silva, Gregor Laimer, Peter Schullian, Yannick Scharll, Alexandra M Dunker, Caleb S O'Connor, Kyle A Jones, Kristy K Brock, Reto Bale, Bruno C Odisio, Iwan Paolucci

Faculty, Staff and Student Publications

Objective: To compare the predictive value of minimal ablative margin (MAM) quantification using tumor segmentation on intraprocedural contrast-enhanced hepatic arterial (HAP) versus portal venous phase (PVP) CT on local outcomes following percutaneous thermal ablation of colorectal liver metastases (CRLM).

Methods: This dual-center retrospective study included patients undergoing thermal ablation of CRLM with intraprocedural preablation and postablation contrast-enhanced CT imaging between 2009 and 2021. Tumors were segmented in both HAP and PVP CT phases using an artificial intelligence-based auto-segmentation model and reviewed by a trained radiologist. The MAM was quantified using a biomechanical deformable image registration process. The area under the …

Machine-Learning Driven Strategies For Adapting Immunotherapy In Metastatic Nsclc, Maliazurina B Saad, Qasem Al-Tashi, Lingzhi Hong, Vivek Verma, Wentao Li, Daniel Boiarsky, Shenduo Li, Milena Petranovic, Carol C Wu, Brett W Carter, Girish S Shroff, Tina Cascone, Xiuning Le, Yasir Y Elamin, Mehmet Altan, Simon Heeke, Ajay Sheshadri, Joe Y Chang, Percy P Lee, Zhongxing Liao, Don L Gibbons, Ara A Vaporciyan, J Jack Lee, Ignacio I Wistuba, Cara Haymaker, Seyedali Mirjalili, David Jaffray, Justin F Gainor, Yanyan Lou, Alessandro Di Federico, Federica Pecci, Mark Awad, Biagio Ricciuti, John V Heymach, Natalie I Vokes, Jianjun Zhang, Jia Wu

Faculty, Staff and Student Publications

Immune checkpoint inhibitors (ICIs), either as monotherapy (ICI-Mono) or combined with chemotherapy (ICI-Chemo), improves survival in advanced non-small cell lung cancer (NSCLC). However, prospective guidance for choosing between these options remains limited, and single-feature biomarkers like PD-L1 prove inadequate. We develop a machine learning model using clinicogenomic data from four cohorts (MD Anderson n = 750; Mayo Clinic n = 80; Dana-Farber n = 1077; Stand Up To Cancer n = 393) to predict individual benefit from adding chemotherapy. Benefit scores are calculated using five distinct functions derived from 28 genomic and 6 clinical features. Our integrated model, A-STEP (Attention-based …

Kids Exploring The World With Chatbots, Maggie Mckay, Mark Connelly

Parent-ish Podcast

Are your kids chatting away with AI? In this episode, we provide parents with the tools they need to understand the implications of children's interactions with chatbots. Find out what signs to look for and how to set healthy boundaries to protect your child from potential pitfalls of digital companionship.

Click here to stream the podcast episode.

Infectious Scleritis: A Comprehensive Narrative Review Of Epidemiology, Clinical Characteristics, And Management Strategies, Hamidreza Ghanbari, Masoud Rahimi, Ali Momeni, Kiana Hassanpour, Nikoo Bayan, Karen E. Lee, Alex Hansen, Ali R. Djalilian, Christopher J. Rapuano, Mohammad Soleimani

Wills Eye Hospital Papers

This study aims to provide an update on infectious scleritis (IS). A comprehensive search was conducted using Google Scholar, Scopus, and PubMed. IS is a rare but critical condition that presents significant diagnostic challenges and often leads to poor visual outcomes. It accounts for approximately 5%-10% of scleritis cases and warrants significant attention due to its delayed diagnosis. Ocular surgery is the primary contributor to IS, accounting for a substantial proportion of cases ranging from 58% to 83%, followed by trauma contributing to approximately 10% of cases. IS can be caused by various microorganisms, including bacteria (86%-87%), fungi (11%-13%), viruses, …

The Microtubule-Severing Enzyme Spastin Regulates Spindle Dynamics To Promote Chromosome Segregation In Trypanosoma Brucei, Thiago Souza Onofre, Qing Zhou, Ziyin Li

Faculty, Staff and Student Publications

Microtubule-severing enzymes play essential roles in diverse cellular processes, including mitosis and cytokinesis, by modulating microtubule dynamics. In the early branching Trypanosoma brucei, microtubule-severing enzymes are involved in cytokinesis and flagellum length control, but none of them have been found to regulate mitosis. Here we report the characterization of the microtubule-severing enzyme spastin in the procyclic form of T. brucei. We demonstrate that spastin severs microtubule in vitro and overexpression of spastin disrupts spindle microtubules in vivo in trypanosomes, leading to defective chromosome segregation. Knockdown of spastin impairs spindle integrity and disrupts chromosome alignment and segregation. We further show that …

Act With Nmosd: A Targeted, Telehealth-Delivered Mental Health Intervention For Patients & Caregivers, Darcy C. Esiason, Patrick J. Smith, Charles L. Peppers, Emily Wakschal, Leigh Andrews, Chelsi N. Nurse, Hallie M. Kushner, Christopher F. Drescher, Heather Bruschwein, Wendy Erler, Tom Hattrich, Ankita Deshpande, Michael Levy, Thomas P. Leist, C. Virginia O'Hayer

Department of Psychiatry and Human Behavior Faculty Papers

PURPOSE: The rare, unpredictable, debilitating nature of neuromyelitis optica spectrum disorder (NMOSD) constitutes a unique psychological burden. This single-arm, pilot clinical trial examined the effectiveness of Acceptance and Commitment Therapy (ACT) tailored to meet the psychological burden of NMOSD, a brief telehealth-delivered intervention, targeting this burden.

METHODS: Forty-three adults with NMOSD (76 % aquaporin-4 seropositive (AQP4+)) in USA, with elevated anxiety and/or depression completed 6-weeks of an experiential talk therapy designed to increase psychological flexibility and valued action, specifically tailored to address the psychological burden of NMOSD: Acceptance and Commitment Therapy (ACT) w NMOSD. Patients attended via Zoom, along with …

Amaurosis Fugax Progressing To Retinal Artery Occlusion With Anterior Migration Of A Retrobulbar Embolus On Orbital Color Doppler Imaging, Ari H. August, Turner D. Wibbelsman, Erik Massenzio, Sarah E. Thornton, Danijel J. Peričić

Wills Eye Hospital Papers

PURPOSE: Orbital color Doppler imaging (CDI) is useful in the evaluation of sudden monocular vision loss, providing information on etiology which may guide management. We present two cases of amaurosis fugax progressing to retinal artery occlusion (RAO) associated with migration of a hyperechoic particle within the central retinal artery (CRA) and altered vascular dynamics found on CDI.

OBSERVATIONS: Both patients presented with amaurosis fugax, and CDI revealed a hyperechoic particle 2.8 mm from the optic nerve head in both patients. Patient 1 was found to have severe aortic stenosis and a thoracic aortic aneurysm and was managed with dual antiplatelet …

Fractional Flow Reserve From Coronary Ct: Evidence, Applications, And Future Directions, Arta Kasaeian, Mohadese Ahmadzade, Taylor Hoffman, Mohammad Ghasemi-Rad, Anoop Padoor Ayyappan

Faculty, Staff and Students Publications

Coronary computed tomography angiography (CCTA) has emerged as the leading noninvasive imaging modality for the assessment of coronary artery disease (CAD), offering high-resolution visualization of the coronary anatomy and plaque characterization. The development of fractional flow reserve derived from CCTA (FFR-CT) has further transformed the diagnostic landscape by enabling the simultaneous evaluation of both anatomical stenosis and lesion-specific ischemia. FFR-CT has demonstrated diagnostic accuracy comparable to invasive FFR. The combined use of CCTA and FFR-CT is now pivotal in a broad range of clinical scenarios, including the evaluation of stable and acute chest pain, assessment of high-risk and complex plaque …