Digital Commons Network^™

A Computer Vision And Machine Learning Approach To Classify Views In Distal Radius Radiographs, Rohan Vemu, Dion Birhiray, Bassem Darwish, Raven Hollis, Sai Unnam, Srikhar Chilukuri, Lorenzo Deveza

Faculty, Staff and Students Publications

Advances in computer vision and machine learning have augmented the ability to analyze orthopedic radiographs. A critical but underexplored component of this process is the accurate classification of radiographic views and localization of relevant anatomical regions, both of which can impact the performance of downstream diagnostic models. This study presents a deep learning object detection model and mobile application designed to classify distal radius radiographs into standard views-anterior-posterior (AP), lateral (LAT), and oblique (OB)- while localizing the anatomical region most relevant to distal radius fractures. A total of 1593 deidentified radiographs were collected from a single institution between 2021 and …

Information Theory Analysis Of Ctx Shows Consistent Clinical Presentation, Jennifer Hanson, Penelope E Bonnen

Faculty, Staff and Students Publications

Cerebrotendinous xanthomatosis (CTX) is a rare, metabolic disorder caused by pathogenic variants in CYP27A1. The classic clinical presentation includes infantile-onset chronic diarrhea, juvenile-onset bilateral cataracts, with development of tendon xanthomas and progressive neurological dysfunction. These multisystem clinical features typically appear in different decades of life often confounding diagnosis of CTX. Further complicating diagnosis is the generally held belief that the clinical presentation of CTX varies highly between individuals and even within families. We applied information theory analyses to CTX patient data to quantitatively assess clinical variability in CTX. We conducted a systematic review of the literature to identify all CTX …

Mutations In The Key Autophagy Tethering Factor Epg5 Link Neurodevelopmental And Neurodegenerative Disorders Including Early-Onset Parkinsonism, Hormos Salimi Dafsari, Celine Deneubourg, Kritarth Singh, Reza Maroofian, Zita Suprenant, Ay Lin Kho, Neil J Ingham, Karen P Steel, Preethi Sheshadri, Franciska Baur, Lea Hentrich, Birgit Gerisch, Mina Zamani, Cesar Alves, Ata Siddiqui, Haidar S Dafsari, Mehri Salari, Anthony E Lang, Michael Harris, Alice Abdelaleem, Saeid Sadeghian, Reza Azizimalamiri, Hamid Galehdari, Gholamreza Shariati, Alireza Sedaghat, Jawaher Zeighami, Daniel Calame, Dana Marafi, Ruizhi Duan, Adrian Boehnke, Gary D Clark, Jill A Rosenfeld, Carrie A Mohila, Dora Steel, Saurabh Chopra, Suvasini Sharma, Nicolai Kohlschmidt, Steffi Patzer, Afshin Saffari, Darius Ebrahimi-Fakhari, Büşra Eser Çavdartepe, Irene J Chang, Erika Beckman, Renate Peters, Andrew Paul Fennell, Bernice Lo, Luisa Averdunk, Felix Distelmaier, Martina Baethmann, Frances Elmslie, Kairit Joost, Sheela Nampoothiri, Dhanya Yesodharan, Hanna Mandel, Amy Kimball, Antonie D Kline, Cyril Mignot, Boris Keren, Vincent Laugel, Katrin Õunap, Kalpana Devadathan, Frederique M C Van Berkestijn, Arpana Silwal, Saskia Koene, Sumit Verma, Mohammed Yousuf Karim, Chahynez Boubidi, Majid Aziz, Gehad Elghazali, Lauren Mattas, Mohammad Miryounesi, Farzad Hashemi-Gorji, Shahryar Alavi, Nayereh Nouri, Mehrdad Noruzinia, Saeideh Kavousi, Arveen Kamath, Sandeep Jayawant, Russell Saneto, Nourelhoda A Haridy, Pinar Ozkan Kart, Ali Cansu, Madeleine Joubert, Claire Beneteau, Kyra E Stuurman, Martina Wilke, Tahsin Stefan Barakat, Homa Tajsharghi, Annarita Scardamaglia, Sadeq Vallian, Semra Hız, Ali Shoeibi, Reza Boostani, Narges Hashemi, Meisam Babaei, Norah Saleh Alsaleh, Julie Porter, Tania Attié-Bitach, Pauline Marzin, Dorota Wicher, Jessica I Gold, Elisabeth Schuler, Amna Kashgari, Rakan F Alanazi, Wafaa Eyaid, Marc Engelen, Mirjam Langeveld, Burkhard Stüve, Yun Li, Gökhan Yigit, Bernd Wollnik, Mariana H G Monje, Dimitri Krainc, Niccolò E Mencacci, Somayeh Bakhtiari, Michael Kruer, Emanuela Argilli, Elliott Sherr, Yalda Jamshidi, Ehsan Ghayoor Karimiani, Yiu Wing Sunny Cheung, Ivan Karin, Giovanni Zifarelli, Peter Bauer, Wendy K Chung, James R Lupski, Manju A Kurian, Jörg Dötsch, Jürgen-Christoph Von Kleist-Retzow, Thomas Klopstock, Matias Wagner, Calvin Yip, Andreas Roos, Rita Carsetti, Carlo Dionisi-Vici, Mathias Gautel, Michael R Duchen, Adam Antebi, Henry Houlden, Manolis Fanto, Heinz Jungbluth

Faculty, Staff and Students Publications

Objective: Autophagy is a fundamental biological pathway with vital roles in intracellular homeostasis. During autophagy, defective cargoes including mitochondria are targeted to lysosomes for clearance and recycling. Recessive truncating variants in the autophagy gene EPG5 have been associated with Vici syndrome, a severe early-onset neurodevelopmental disorder with extensive multisystem involvement. Here, we aimed to delineate the extended, age-dependent EPG5-related disease spectrum.

Methods: We investigated clinical, radiological, and molecular features from the largest cohort of EPG5-related patients identified to date, complemented by experimental investigation of cellular and animal models of EPG5 defects.

Results: Through worldwide collaboration, we identified 211 patients, 97 …

Cognitive Reserve Predicts Baseline Tau Burden In The Us Pointer Trial Imaging Cohort, Valory N Pavlik, Chris J Weber, Joseph C Masdeu, Laura D Baker, Melissa M Yu, Michele York, Rachel A Whitmer, Susan M Landau, Theresa M Harrison, Tomas M Holland, Laura Lovato

Faculty, Staff and Students Publications

Introduction: Higher cognitive reserve (CR) is associated with reduced dementia risk. We hypothesized that higher CR is associated with less baseline Alzheimer's disease (AD) pathology in the U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) cohort.

Methods: A subsample of participants underwent amyloid beta and tau positron emission tomography imaging. Regression analysis was used to model the association between educational attainment (EA) as a CR proxy measure, amyloid positivity, and entorhinal cortex (ERC) and meta-temporal region of interest (meta-ROI) tau standardized uptake value ratio (SUVR).

Results: In 911 participants with complete imaging data, higher …

Deciphering Rna Modification And Post-Transcriptional Regulation With Netrnapan, Haodong Xu, Wankun Deng, Ruifeng Hu, Binfeng Liu, Wenchao Zhang, Lujuan Wang, Lin Qi, Xiaolei Ren, Chao Tu, Zhihong Li, Zhongming Zhao

Faculty, Staff and Student Publications

RNA modification, which is evolutionarily conserved, is crucial for modulating various biological functions and disease pathogenesis. High resolution transcriptome-wide mapping of RNA modifications has facilitated both data resources and computational prediction of RNA modification. While these prediction algorithms are promising, they are limited in interpretability or generalizability, or the capacity for discovering novel post-transcriptional regulations. Here, we present NetRNApan, a deep learning framework for RNA modification site prediction, motif discovery and trans-regulatory factor identification. Using m5U profiles generated by FICC-seq and miCLIP-seq technologies and single-base resolution m6A sites from multiple experiments as cases, we demonstrated the accuracy of NetRNApan with …

Exploring Multimodal Large Language Models On Transthoracic Echocardiogram (Tte) Tasks For Cardiovascular Decision Support, Jianfu Li, Yiming Li, Zenan Sun, Evan Yu, Ahmed M Abdelhameed, Weiguo Cao, Haifang Li, Jianping He, Pengze Li, Jingna Feng, Yue Yu, Xinyue Hu, Manqi Li, Rakesh Kumar, Yifang Dang, Fang Li, Shahyar M Gharacholou, Cui Tao

Faculty, Staff and Student Publications

Objective: Multimodal large language models (LLMs) offer new potential for enhancing cardiovascular decision support, particularly in interpreting echocardiographic data. This study systematically evaluates and benchmarks foundation models from diverse domains on echocardiogram-based tasks to assess their effectiveness, limitations and potential in clinical cardiovascular applications.

Methods: We curated three cardiovascular imaging datasets-EchoNet-Dynamic, TMED2, and an expert-annotated echocardiogram (TTE) dataset-to evaluate performance on four critical tasks: (1) cardiac function evaluation through ejection fraction (EF) prediction, (2) cardiac view classification, (3) aortic stenosis (AS) severity assessment, and (4) cardiovascular disease classification. We evaluated six multimodal LLMs: EchoClip (cardiovascular-specific), BiomedGPT and LLaVA-Med (medical-domain), and …

Hand Swelling And Other Non-Raynaud Phenomenon Symptoms As The Initial Presentation Of Systemic Sclerosis: Prevalence And Clinical Associations In Two Us Cohorts, Iqtidar Hanif, Shervin Assassi, Maureen D Mayes, Zsuzsanna H Mcmahan, Meng Zhang, Julio Charles, John M Vanburen, Jessica S Alvey, Kimia Ghaffari, Elana J Bernstein, Flavia V Castelino, Lorinda Chung, Luke Evnin, Tracy M Frech, Jessica K Gordon, Faye N Hant, Laura K Hummers, Dinesh Khanna, Kimberly S Lakin, Dorota Lebiedz-Odrobina, Yiming Luo, Ashima Makol, Jerry A Molitor, Duncan F Moore, Carrie Richardson, Nora Sandorfi, Ami A Shah, Ankoor Shah, Victoria K Shanmugam, Virginia D Steen, Elizabeth R Volkmann, Carleigh Zahn, Brian Skaug

Faculty, Staff and Student Publications

Objective: Raynaud phenomenon (RP) is often the initial clinical manifestation of systemic sclerosis (SSc), but some patients develop other manifestations first. To help elucidate the diversity of SSc presentation in its early stages, we describe the initial clinical manifestations and antinuclear antibody (ANA) profiles of patients in two early SSc cohorts.

Methods: All patient data in the Genetics vs Environment in Scleroderma Outcomes Study (GENISOS) and Collaborative National Quality and Efficacy Registry (CONQUER) cohorts were reviewed. Both studies enrolled patients within five years of the first non-RP symptom.

Results: In GENISOS and CONQUER, respectively, 194 (44.2%) of 439 and 292 …

Study Of 18 F-Fluciclovine Pet For Serial Assessment Of Glioblastoma Tumor Volumes During Surgery And Radiotherapy, Samir A Dagher, Jason M Johnson, Rania M M Mohamed, Shehbaz Ansari, Osama Mawlawi, Ho-Ling Liu, Max Wintermark, Dawid Schellingerhout, Lesley Flynt, Debra N Yeboa, Jeffrey S Weinberg, Sherise D Ferguson, Maria K Gule-Monroe

Faculty, Staff and Student Publications

PURPOSE: Recent evidence supports incorporating 18 F-Fluciclovine PET for glioblastoma treatment planning and monitoring, as it better captures tumor infiltration compared to conventional MRI. However, the relationship between PET- and MRI-defined tumor volumes remains unclear, particularly in the post-treatment setting. This study prospectively compares tumor volumes on MRI and PET at multiple timepoints throughout the treatment course and evaluates volumetric changes with therapy.

METHODS: We prospectively enrolled 8 adults with IDH-wildtype glioblastoma treated with surgery and chemoradiation between September 2019 and 2021. Participants underwent paired 18 F-Fluciclovine PET/CT and conventional MRI at four timepoints: preoperatively, pre-radiation, and at one- and …

Bilateral Hypoglossal Nerve Stimulation For Obstructive Sleep Apnea: A Nonrandomized Clinical Trial, B. Tucker Woodson, David T. Kent, Colin Huntley, Melyssa K Hancock, Douglas J. Van Daele, Maurits S. Boon, Tod C. Huntley, Sam Mickelson, M. Boyd Gillespie, Maria V. Suurna, Ashutosh Kacker, Asim Roy, Stuart Mackay, Kirk P. Withrow, Raj C. Dedhia, Phillip Huyett, Clemens Heiser, Sylvie Di Nicola, Fatima Makori, Olivier M. Vanderveken, Tapan A. Padyha, Ulysses J. Magalang, Eugene Chio, Eric J. Kezirian, Richard Lewis

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Study Objectives: To evaluate the safety and efficacy of a novel bilateral hypoglossal nerve stimulation (HNS_BL) device for the treatment of obstructive sleep apnea.

Methods: Adult patients with moderate-to-severe obstructive sleep apnea who refused, failed, or did not tolerate positive airway pressure therapy underwent implantation and nightly use of HNS_BL. The coprimary endpoints at 12 months were (1) a minimum of 50% reduction in the 4% apnea-hypopnea index (AHI) from baseline with a final AHI of less than 20 events/h, and (2) a minimum of 25% reduction in the 4% oxygen desaturation index. Objective secondary endpoints …

Consequences Of Adverse Events In Cancer Immunotherapy Combinations - A Comprehensive Real-World Analysis, Siv Gyda Aanes, Carsten Nieder, David Westfall Bates, Siri Wiig, Ellinor Christin Haukland

Faculty, Staff and Students Publications

Background: Immune checkpoint inhibitors (ICIs) are pivotal in systemic anticancer therapy. The aim of the study was to investigate incidence, severity and consequences of immune-related adverse events (irAEs) in ICI combinations by comparing different adverse events classification systems.

Methods: A retrospective multicentre cohort study included patients treated with ICI combinations. IrAEs were assessed by CTCAE v.5, NCC MERP index and SITC consensus for chronic irAEs.

Results: Among 612 patients, 244 (40%) experienced 354 irAEs, in total 58 irAEs per 100 patients varying between treatments. Higher incidence was observed for autoimmune disease, thoracic radiotherapy, melanoma, dual ICI and ICI/TKI. Severe irAEs …

Basal Cell Carcinoma Risk Prediction In Survivors Of Childhood Cancer, Cindy Im, Christina Boull, Zhe Lu, Kenneth Liao, Hasibul Hasan, Linwan Xu, Yadav Sapkota, Rebecca M Howell, Michael A Arnold, Miriam R Conces, Ashley J Housten, Judith Gebauer, Thorsten Langer, Jop C Teepen, Leontien C M Kremer, Louis S Constine, Yutaka Yasui, Melissa M Hudson, Kirsten K Ness, Gregory T Armstrong, Joseph P Neglia, Yan Yuan, Lucie M Turcotte

Faculty, Staff and Student Publications

Background: Survivors of childhood cancer face excess risk of developing basal cell carcinoma. Age-specific basal cell carcinoma risk prediction models for survivors may support targeted screening recommendations.

Methods: We developed models predicting basal cell carcinoma risk by ages 40 and 50 years featuring detailed cancer treatment predictors, utilizing statistical and machine-learning algorithms and data from 23 166 five-year survivors in the Childhood Cancer Survivor Study, a multi-institutional retrospective cohort study. Selected models were externally validated in 5314 survivors in the St Jude Lifetime Cohort. Model discrimination and precision were evaluated using the area under the receiver operating characteristic curve (AUROC) …

Acute Kidney Injury Is Associated With Elevated Urinary Endotrophin, Amanda J Clark, Brenda Mendoza Flores, Marie Christelle Saade, Kyle Q Vu, Isaac J Pence, Ningyan Zhang, Zhiqiang An, Dawei Bu, Philipp E Scherer, Samir M Parikh

Faculty, Staff and Student Publications

Acute kidney injury (AKI) is prevalent among hospitalized patients. Novel biomarkers are needed to diagnose AKI and target therapies. Endotrophin (ETP) is a molecule released during collagen type VI formation that may promote injury and fibrosis. Although serum ETP elevation has been associated with adverse outcomes in AKI, urinary ETP has not been assessed in AKI, nor has ETP been evaluated in a pediatric population. Urine samples were collected from a tertiary children's hospital. Medical records were reviewed, and patients who met criteria were sorted into three categories:

Continuous Androgen Deprivation Therapy With Or Without Metastasis-Directed Therapy For Oligometastatic Prostate Cancer: The Multicenter Phase 2 Randomized Extend Trial, Alexander D Sherry, Bilal A Siddiqui, Cara Haymaker, Bryan M Fellman, Marina N Medina-Rosales, Tharakeswara K Bathala, Shuqi Wang, Suyu Liu, Aaron Seo, Kieko Hara, Hsinyi Lu, Patricia Troncoso, Stephen G Chun, Chul S Ha, Lauren L Mayo, Henry Mok, Ryan J Park, Brian F Chapin, Ryan M Phillips, Matthew P Deek, Craig A Kovitz, Ana Aparicio, Amado J Zurita, Patrick G Pilie, Lorenzo Cohen, Seungtaek L Choi, Alexandre Reuben, Phuoc T Tran, Paul G Corn, Sumit K Subudhi, Chad Tang

Faculty, Staff and Student Publications

Background and objective: Oligometastatic prostate cancer (omPC) is characterized by limited metastases. We hypothesized that metastasis-directed therapy (MDT) to all sites of omPC combined with androgen deprivation therapy (ADT) would improve clinical outcomes.

Methods: In the multicenter phase 2 EXTEND trial, patients with omPC were randomized 1:1 to ADT versus MDT + ADT in two independently powered and randomized baskets, one using intermittent ADT and one using continuous ADT. The primary endpoint was progression-free survival (PFS). The secondary endpoints included radiologic PFS (rPFS) and castration resistance-free survival (CRFS). Here, the primary results of the continuous ADT basket, the combined analysis …

Rank-Based Learning: A Novel High-Throughput Algorithm Resilient To Missing Data And Effective For Datasets With Small Sample Size, Lulu Song, Hamid Khoshfekr Rudsari, Johannes F Fahrmann, Jody Vykoukal, Sam Hanash, James P Long, Kim-Anh Do, Ehsan Irajizad

Faculty, Staff and Student Publications

High-throughput omics data present challenges for binary classification due to platform variability, batch effects, missing values, and high dimensionality. This study presents a novel Rank-Based Learning (RBL) method that leverages relative feature rankings to improve robustness and generalizability. We evaluated RBL against established methods like Logistic Regression (LR) and Random Forest (RF) using simulated data and two real-world plasma proteomics datasets: early-stage small cell lung cancer (SCLC) and duodenopancreatic neuroendocrine tumors (dpNET) in patients with Multiple Endocrine Neoplasia type 1 (MEN1). In simulation experiments, RBL outperformed LR under conditions involving batch effects, missing data, and varying numbers of true differential …

Genome Sequencing Reveals The Impact Of Pseudoexons In Rare Genetic Disease, Georgia Pitsava, Megan Hawley, Light Auriga, Ivan De Dios, Arthur Ko, Sofia Marmolejos, Miguel Almalvez, Ingrid Chen, Kaylee Scozzaro, Jianhua Zhao, Rebekah Barrick, Nicholas Ah Mew, Vincent A Fusaro, Jonathan Lotempio, Matthew Taylor, Luisa Mestroni, Sharon Graw, Dianna Milewicz, Dongchuan Guo, David R Murdock, Kinga M Bujakowska, Changrui Xiao, Emmanuèle C Délot, Seth I Berger, Eric Vilain

Faculty, Staff and Student Publications

Purpose: Advancements in sequencing technologies have significantly improved clinical genetic testing; yet, the diagnostic yield remains around 30% to 40%. Emerging technologies are now being deployed to address the remaining diagnostic gap.

Methods: We tested whether short-read genome sequencing could increase the diagnostic yield in individuals enrolled into the UCI-GREGoR research study, who had suspected Mendelian conditions and prior inconclusive testing. Two other collaborative research cohorts, focused on aortopathy and dilated cardiomyopathy, consisted of individuals who were undiagnosed but had not undergone harmonized prior testing.

Results: We sequenced 353 families (754 participants) and found a molecular diagnosis in 54 (15.3%) …

Women With Persistent Atrial Fibrillation Need More Than Pulmonary Vein Isolation: Personalised Extra-Pulmonary Vein Ablation Strategy Vs. Pulmonary Vein Isolation Alone In The Tailored-Af Trial, Isabel Deisenhofer, Daniel H Cooper, Et Al.

2020-Current year OA Pubs

AIMS: There is still conflicting evidence if women with persistent atrial fibrillation (AF) profit from a pulmonary vein isolation (PVI) plus strategy. We evaluated the efficacy of a spatio-temporal dispersion-targeted ablation strategy in women from the TAILORED-AF trial.

METHODS AND RESULTS: In TAILORED-AF, 370 patients were randomised to either a personalised, artificial intelligence (AI)-guided tailored ablation or to PVI-only. AF substrate mapping data and 12-month ablation outcomes were compared between women and men. Overall, 21% patients were female (70.4 ± 6.9 vs. 64.5 ± 8.5 years for men, P < 0.001). While spatio-temporal dispersion extent was similar between groups, left atrial low-voltage surface area (< 0.2 mV) was significantly larger in women (P < 0.01). In women, the single-procedure freedom from AF (76% vs. 50%, log-rank P < 0.001) and any atrial arrhythmia (56% vs. 38%, log-rank P < 0.05) were significantly superior to PVI alone with a tailored procedure. In the PVI-only group, the single-procedure freedom from AF (50% vs. 70%, log-rank P < 0.001) and any atrial arrhythmia (38% vs. 61%, log-rank P < 0.001) were significantly lower in women. After a tailored ablation, no significant differences were observed between women and men regarding freedom from AF (76% vs. 91%, log-rank P = 0.07) or any atrial arrhythmia (56% vs. 62%, log-rank P = 0.69) free survival.

CONCLUSION: Compared to men, PVI-only in women with persistent AF leads …

How Augmin Establishes The Angle Of The Microtubule Branch Site, Sophie M Travis, Jodi Kraus, Collin T Mcmanus, Kiana Golden, Rui Zhang, Sabine Petry

2020-Current year OA Pubs

How microtubules (MTs) are generated in the proper orientation is essential to understanding how the cytoskeleton organizes a cell and MT-dependent events such as cell division. In the spindle, most MTs are generated through the branching MT nucleation pathway. In this pathway, new MTs are nucleated from the side of existing MTs and oriented at a shallow angle by the branching factor augmin, ensuring that both MTs have the same polarity. Yet, how augmin binds MTs and sets the branch angle has remained unclear. Here, we report the cryo-electron microscopy structure of an augmin subcomplex on the MT. This structure …

Runx2 Cooperates With Srebp1 To Rewire Cancer Metabolism And Promote Aggressiveness, Emanuele Vitale, Mila Gugnoni, Veronica Manicardi, Silvia Muccioli, Federica Torricelli, Benedetta Donati, Simonetta Piana, Gloria Manzotti, Elisa Salviato, Francesca Reggiani, Cristian Ascione, Rebecca Vezzani, Moira Ragazzi, Mattia Forcato, Oriana Romano, Silvio Bicciato, Aaron Goldman, Marco Tigano, Alessia Ciarrocchi

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Embryonic Transcription Factors (TFs) are often reactivated in cancer, driving developmental gene programs that support phenotypic plasticity. Metabolic adaptation fuels this plasticity by supplying energy and molecular building blocks for growth. RUNX2, the master regulator of bone morphogenesis, is ectopically expressed in epithelial cancer, promoting metastasis through trans-differentiation processes like Epithelial-to-Mesenchymal Transition (EMT) and osteomimicry. By combining omics data with functional validation, we demonstrated that RUNX2 drives cancer cell metabolic rewiring by repressing mitochondrial respiration while promoting anabolic processes. We showed that RUNX2 upregulates key genes of lipid biosynthesis by regulating and cooperating with SREBP1. In vivo expression analysis in …

Understanding The Effects Of Real-Time Head Position Feedback On Postural Sway In Terms Of Changes In Underlying Deterministic And Stochastic Dynamical Processes, Steven J. Harrison, Benjamin De Bari, Ryan Poutre, Jeffrey M. Kinsella-Shaw

College of Humanities and Sciences Faculty Papers

Our perceptual systems detect information about how our body is moving relative to the surrounding environment. Such information is essential to our ability to maintain upright standing balance. Real-time postural feedback systems are technologies that appear to enhance our ability to detect information about the movements of our body, and as a consequence improve our capacity to control the posture of our body. Here we examine a system in which real-time measurements of head position were "felt" as changes in the intensity of vibration of tactors in a headband. Using this system, participants were able to stabilize their body posture, …

Complement Activation In Secondary Thrombotic Microangiopathies, Johann Morelle, Fernando Caravaca-Fontan, Fadi Fakhouri, Eleni Frangou, Annette Bruchfeld, Jürgen Floege, Safak Mirioglu, Sarah M Moran, Stefanie Steiger, Kate I Stevens, Onno Y K Teng, Selda Aydin, Anuja Java, Sjoerd A M E G Timmermans, Andreas Kronbichler

2020-Current year OA Pubs

Secondary thrombotic microangiopathies (TMAs) represent a heterogeneous group of diseases associated with a high risk of kidney failure and death despite available therapeutic strategies. Strong evidence implicates complement activation in the pathogenesis of secondary TMA, and emerging data increasingly suggest that pharmacological blockade of the complement improves the outcomes in patients with secondary TMA. Certain forms of secondary TMA, including postpartum TMA, TMA with coexisting hypertensive emergency and de novo TMA after kidney transplantation exhibit a high prevalence of pathogenic variants in complement genes, similar to those observed in primary atypical haemolytic uraemic syndrome. These conditions should be considered as …

Comparing In-Person And Remote Consent Of People With Dementia Into A Primary Care-Based Cluster Randomised Controlled Trial: Lessons From The Dementia Personalised Care Team (D-Pact) Feasibility Study, T. M. Oh, S. Batool, C. Musicha, L. Greene, H. Wheat, L. Smith, S. Griffiths, A. Gude, L. Weston, H. Shafi, K. Stevens, C. Sutcliffe, W. Taylor, W. Ingram, B. Hussain, P. Clarkson, I. Sherriff, O. C. Ukoumunne, S. Creanor, R. Byng

Peninsula Medical School

Background: Complex socio-cultural, psychological, geographical, and service-related challenges are faced when recruiting people with dementia for clinical trials. The aim of Phase 1 of the Dementia PersonAlised Care Team (D-PACT) project was to assess the feasibility of recruiting (identifying, approaching and consenting) people with dementia, including those without capacity to consent, to a cluster randomized controlled trial of a primary care-based personalized dementia support intervention in England. COVID-19 necessitated a shift to remote working, creating the opportunity to compare recruitment strategies before and under lockdown constraints. This paper shares the adaptations made to enable remote consent and capacity judgement with …

The Regulation Of The Hippo Signalling Pathway Effector Yap Through A Novel Lipid-Dependent Extracellular Matrix Complex, Simge Karagil, Natalia Haddad, Michael Stolinski, Natasha Hill, Darren Johnson, Nadine Wehida, Ahmed Elbediwy

School of Biomedical Sciences

Lipid metabolism plays a significant role in the regulation of various critical pathways within cells, where enhanced lipid metabolism is a hallmark of cancer cell metabolism. The Hippo signalling pathway poses as an important signalling pathway that governs tissue growth control and tumorigenesis. The effector of the Hippo signalling pathway, Yes-associated protein (YAP), serves as a central regulator for this growth control. Once a tissue develops to its correct size, YAP is phosphorylated and inactivated within the cytoplasm by the activation of the Hippo pathway, where its inactivation results in YAP nucleus translocation. This allows its dephosphorylation, modulating various cellular …

Accessible, Realistic Genome Simulation With Selection Using Stdpopsim., Graham Gower, Nathaniel S Pope, Murillo F Rodrigues, Silas Tittes, Linh N Tran, Ornob Alam, Maria Izabel A Cavassim, Peter D Fields, Benjamin C Haller, Xin Huang, Ben Jeffrey, Kevin Korfmann, Christopher C Kyriazis, Jiseon Min, Inés Rebollo, Clara T Rehmann, Scott T Small, Chris C R Smith, Georgia Tsambos, Yan Wong, Yu Zhang, Christian D Huber, Gregor Gorjanc, Aaron P Ragsdale, Ilan Gronau, Ryan N Gutenkunst, Jerome Kelleher, Kirk E Lohmueller, Daniel R Schrider, Peter L Ralph, Andrew D Kern

Faculty Research 2025

Selection is a fundamental evolutionary force that shapes patterns of genetic variation across species. However, simulations incorporating realistic selection along heterogeneous genomes in complex demographic histories are challenging, limiting our ability to benchmark statistical methods aimed at detecting selection and to explore theoretical predictions. stdpopsim is a community-maintained simulation library that already provides an extensive catalog of species-specific population genetic models. Here, we present a major extension to the stdpopsim framework that enables simulation of various modes of selection, including background selection, selective sweeps, and arbitrary distributions of fitness effects (DFE) acting on annotated subsets of the genome (for instance, …

Brca2 Deficiency And Replication Stress Drive Apobec3-Mediated Genomic Instability, Kathy Situ, Abby M Green, Et Al.

2020-Current year OA Pubs

BRCA2 plays a critical role in stabilizing stalled replication forks, yet critical gaps remain in understanding how BRCA2 deficiency triggers fork collapse and drives genomic instability. Here, we identify cytidine deaminase APOBEC3B as a key driver of this process. Using a unique uracil-in-DNA probe, we show that BRCA2 loss promotes APOBEC3B-mediated uracil accumulation in single-stranded DNA (U-ssDNA) at stalled forks. These lesions when processed by UNG2 and APE1, trigger fork collapse and release ssDNA fragments into the cytoplasm, activating NF-κB signaling. This in turn upregulates APOBEC3B expression, establishing a self-reinforcing loop that amplifies cytidine deamination at stalled forks and exacerbates …

Sexual Activity And Functioning After Breast Cancer Treatment: Perspectives On The Importance Of Pleasure From A Radiotherapy Cohort, Melanie Besculides, Lauren Carney, Ksenia Gorbenko, Sheryl Green, Melissa Brito, Jezelle Lynch, Carly Feldman, Cindy Munoz, Madhu Mazumdar, Deborah C. Marshall

Student Papers, Posters & Projects

BACKGROUND: Breast cancer affects millions of women and while treatment can be lifesaving, it also has numerous side effects, including those related to sexual function, which often impact the ability to experience pleasure from sex. This study aimed to understand how breast cancer survivors define sexual activity, identify important aspects, and ascertain perceived impacts of treatment on sexual activity and function, particularly related to pleasure.

METHODS: Semi-structured interviews were conducted with women who were breast cancer survivors at least one-year post-radiation. Priority populations were oversampled (racial/ethnic/sexual/gender minorities, those aged over 65 or under 45). The sample included 23 participants: 11 …

Short Term Hemodynamic Effects Of Atrial Fibrillation In A Closed-Loop Human Cardiac-Baroreflex System, Oluwasanmi Adeodu, Michelle Gee, Babak Mahmoudi, Rajanikanth Vadigepalli, Mayuresh V. Kothare

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Atrial fibrillation (AF) remains the leading cardiac cause of stroke and AF-related death rate in the United States has been increasing for over twenty years. While the effect of standalone AF on heart rate is well established, there is a lack of clarity on its impact on other critical hemodynamic metrics. This is ostensibly due to interaction with other common comorbidities, especially hypertension. In addition, AF has a complex relationship with the state of the baroreflex. Evidence indicates that baroreflex sensitivity (BRS), the ability of the intrinsic cardiac control system to initiate parasympathetic response, is suppressed during AF. Therefore, a …

Impact Of Transplant Conditioning, Npm1 Mutations, And Measurable Residual Disease In Flt3-Itd Acute Myeloid Leukemia, Mark J Levis, Geoffrey L Uy, Et Al.

2020-Current year OA Pubs

We conducted a post hoc analysis of data from Blood and Marrow Transplant Clinical Trials Network 1506 (MORPHO), a randomized trial of gilteritinib vs placebo as posttransplantation maintenance for patients with FLT3-ITD-mutated acute myeloid leukemia (AML) undergoing allogeneic hematopoietic cell transplantation (HCT), focusing the interactions between conditioning regimen intensity, measurable residual disease (MRD), and NPM1 comutation status reported from diagnosis. Comparing FLT3-ITD MRD before and after conditioning, there was no difference between myeloablative conditioning (MAC) and reduced-intensity conditioning (RIC) in eradication or reduction of FLT3-ITD MRD. For participants who were FLT3-ITD MRD negative before HCT, there was no difference in …

Real-World Data For Tisagenlecleucel In Patients With R/R B-All: Subgroup Analyses From The Cibmtr Registry., Samuel John, Kevin J. Curran, Erin Hall, Amy K. Keating, Susanne H C Baumeister, Sarah Nikiforow, Timothy Driscoll, Amy Moskop, Kevin O. Mcnerney, Christine L. Phillips, Michael A. Pulsipher, Emily M. Hsieh, Rayne H. Rouce, Marcelo C. Pasquini, Ranjan Tiwari, Jennifer Willert, Roberto Ramos, Joerg Krueger, Erin Guest, Stephan A. Grupp

Manuscripts, Articles, Book Chapters and Other Papers

Since the first approval of tisagenlecleucel in 2017, pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) may receive this CD19-directed chimeric antigen receptor T-cell therapy. We report real-world data from the Center for International Blood and Marrow Transplant Research (>2.5 years of follow-up). As of 4 May 2022, 768 patients with B-ALL had received tisagenlecleucel. Patients aged ≥18 and < 18 years of age (including those < 3 years) were treated during first relapse (26.6% and 26.7% [< 3 years, 44.8%], respectively) or primary refractory disease (12.4% and 12.1% [< 3 years, 15.5%], respectively) with 17.6% and 11.6% (< 3 years, 13.8%), respectively, having high disease burden (≥50% bone marrow [BM] blasts) and 20.2% and 20.2% (< 3 years, 13.8%), respectively, having low disease burden (>0 to < 5% BM blasts). Among patients with ≥12 months postinfusion follow-up (n = 578; median follow-up, 32.1 months), the best overall response of complete remission/complete remission with incomplete blood count recovery was 86.0%. The 12-month relapse-free survival (RFS) and overall survival (OS) were 61.8% and 79.4%, respectively, whereas the 24-month RFS and OS were 50.3% and 63.8%, respectively. Age (< 18 years) and disease burden (< 50% BM blasts) were associated with better outcomes. Previous inotuzumab therapy and KMT2A rearrangement were associated with worse outcomes. Older patients (≥18 years) experienced a higher rate of any-grade cytokine release syndrome (CRS) associated with higher disease burden before infusion. Any-grade CRS and neurotoxicity were lower in patients aged < 3 years. Extended follow-up continues to demonstrate high rates of RFS and favorable safety in this population.

Effect Of Valemetostat On The Pharmacokinetics Of Midazolam And Digoxin: A Phase 1 Drug-Drug Interaction Study In Patients With Non-Hodgkin Lymphoma, Masaya Tachibana, Steven Horwitz, Eric Jacobsen, Francine Foss, Pamela Allen, Pierluigi Porcu, Tatyana Feldman, Jia Ruan, Jonathan Brammer, Jie Wang, Shinichi Inaba, Yuka Iko, Keiko Nakajima, Yasuyuki Kakurai, Noriaki Kitami, Yang Chen, Yvonne Lau

Department of Medicine Faculty Papers

Valemetostat tosylate (valemetostat) is an oral, potent, dual inhibitor of enhancer of zeste homolog (EZH)2/1, under investigation in non-Hodgkin lymphomas (NHLs) and solid tumors. In vitro, it inhibits cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp) when combined with sensitive CYP3A or P-gp substrates. This drug–drug interaction (DDI) sub-study is part of the phase 1 trial of valemetostat monotherapy (DS3201-A-J101; NCT02732275), assessing the effect of valemetostat on the pharmacokinetics (PK) of sensitive CYP3A and P-gp substrates midazolam and digoxin, respectively, in patients with relapsed or refractory NHL, and its safety and efficacy. Patients received two simultaneous single doses of midazolam and …

Adherence To Integrative Care, Oncology Healthcare Utilization, Opioid Use And Hospitalization, Eran Ben-Arye, Dan Greenberg, Noah Samuels, Ana Maria Lopez, Tzahit Simon-Tuval

Kimmel Cancer Center Faculty Papers

Research on the relationship between integrative oncology (IO) programs and dispensing of chemotherapy agents and supportive care drugs, and hospitalization rates is limited. The present study examined these outcomes in chemotherapy-treated patients with cancer, comparing patients highly adherent to integrative care (high-AIC) to those with low adherence (low-AIC). Data from patients with cancer treated with taxane and/or platinum-based agents participating in an ongoing prospective, controlled pragmatic trial were examined retrospectively. Patients were referred to an IO consultation and weekly treatments at 3 medical centers in Northern Israel, with high-AIC defined as attending ≥4 sessions at 6 weeks; low-AIC, 0-3 sessions. …