Digital Commons Network^™

All Genetic Subtypes Of B-Cell Acute Lymphoblastic Leukemia Exhibit Increased Incidence Rates In Children With Down Syndrome, Ching-Ju Hsu, Jeremy M Schraw, Tania A Desrosiers, Amanda E Janitz, Russell S Kirby, Eirini Nestoridi, Wendy N Nembhard, Jason L Salemi, Charles Shumate, Jean Paul Tanner, Mahsa M Yazdy, Michael E Scheurer, Karen R Rabin, Philip J Lupo

Faculty, Staff and Students Publications

No abstract provided.

A Phenotypic Screen Identifies Xanthohumol And Other Flavonoids As Killers Of Bladder Cancer, Michael J Bolt, Jessica Oceguera, Alejandra Rivera Tostado, Christopher D Candler, Elina Mosa, Kazem Safari, Maureen G Mancini, Michael A Mancini

Faculty, Staff and Students Publications

Bladder cancer accounts for 4 % of cancer diagnoses in the US. Current treatments primarily involve trans-urethral resection of bladder tumors (TURBT) and immunotherapy with Bacille Calmette-Guerin (BCG). Despite the efficacy of TURBT, issues with residual tumors persist. We chose to utilize Cell Painting to screen a set of 244 flavonoid compounds for bladder cancer cell toxicity. Using multiparametric high content analysis termed SPACe, we discover promising candidates underscoring the potential of flavonoids in targeting bladder cancer cells and elucidating their mechanisms of action. Notably, compounds such as xanthohumol show promise in reducing cancer cell viability by altering lipid metabolism. …

Barriers To And Facilitators Of Sustaining A Systemic Lupus Erythematosus (Sle) Patient Decision Aid In Regular Rheumatology Outpatient Care In The Usa, Erin E Blanchard, Allyson G Hall, Ezra Gore, Parvaneh Yaghoubi Jami, Aizhan Karabukayeva, Larry R Hearld, Shelby Gontarz, Jasvinder A Singh

Faculty, Staff and Students Publications

Objective: This study investigates the barriers to and facilitators of sustaining a decision aid (DA) tool for patients with SLE in routine rheumatology outpatient care across the USA. The DA was initially developed for assisting patients with SLE in making informed medication choices by providing personalized information on their treatment process.

Methods: We conducted semi-structured interviews with clinicians, administrators, and information technology (IT) professionals from 15 geographically diverse rheumatology clinics that participated in a large-scale DA implementation trial. Interviews were transcribed and analysed using NVivo, with thematic coding to identify key factors influencing DA sustainability.

Results: The analysis identified several …

Injectable Ionic Hydrogel Conductors: Advancing Material Design To Transform Cardiac Pacing, Gabriel J Rodriguez-Rivera, Allison Post, Mathews John, Derek Bashe, Fei Xu, Trace Larue, Abbey Nkansah, Megan Wancura, Malgorzata Chwatko, Christina Waldron, Nikhith Kalkunte, Janet Zoldan, Mathieu Arseneault, Abdou Elgalad, Manuel K Rausch, Mehdi Razavi, Elizabeth Cosgriff-Hernandez

Faculty, Staff and Students Publications

Direct pacing of the mid myocardium where re-entry originates can be used to prevent ventricular arrhythmias and circumvent the need for painful defibrillation or cardiac ablation. However, there are no pacing electrodes small enough to navigate the coronary veins that cross these culprit scar regions. To address this need, we have developed an injectable ionically conductive hydrogel electrode that can fill the epicardial coronary veins and transform them into flexible electrodes. A new hydrogel chemistry based on a polyether urethane diacrylamide macromer was developed that matches myocardial stiffness and is resistant to hydrolysis. Conductivity was imparted using ionic precursor solutions …

Cost Analysis Of Antiarrhythmic Drug Monitoring In Patients Hospitalized With Atrial Fibrillation And Flutter, Abdul Mannan Khan Minhas, Taha Mansoor, Mohamed M Gad, Mihail G Chelu, Jalaj Garg, Dmitry Abramov

Faculty, Staff and Students Publications

No abstract provided.

Conduction System Pacing Compared With Biventricular Pacing For Cardiac Resynchronization Therapy In Patients With Heart Failure And Mildly Reduced Left Ventricular Ejection Fraction: Results From International Collaborative Lbbap Study (I-Clas) Group, Pugazhendhi Vijayaraman, Francesco Zanon, Shunmuga Sundaram Ponnusamy, Bengt Herweg, Parikshit Sharma, Manuel Molina-Lerma, Marek Jastrzębski, Zachary Whinnett, Kevin Vernooy, Rajeev K Pathak, Roderick Tung, Gaurav Upadhyay, Karol Curila, Dipen Zalavadia, Nischay Shah, Lina Marcantoni, Mohamed Gad, Ramez Morcos, Pawel Moskal, Akriti Naraen, Mishal Mumtaz, Jamario R Skeete, Praneet S Katrapati, Jeffrey Kolominsky, Johan Van Koll, Mihail G Chelu, Kenneth A Ellenbogen, Oscar Cano

Faculty, Staff and Students Publications

Background: Cardiac resynchronization therapy (CRT) is a guideline-recommended therapy in patients with heart failure with mildly reduced ejection fraction (HFmrEF, 36%-50%) and left bundle branch block or indication for ventricular pacing. Conduction system pacing (CSP) using left bundle branch area pacing or His bundle pacing has been shown to be a safe and physiologic alternative to biventricular pacing (BVP).

Objective: The aim of this study was to compare the clinical outcomes between BVP and CSP for patients with HFmrEF undergoing CRT.

Methods: Consecutive patients who underwent BVP or CSP with HFmrEF between January 2018 and June 2023 at 16 international …

A Farewell Message, Misty L. Rhoads

Journal of Transformative Touch

No abstract provided.

Anti-Viral Cd8 Central Memory Veto Cells As A New Platform For Car T Cell Therapy, Wei-Hsin Liu, Anat Globerson Levin, Assaf Lask, Galit Horn, Tova Waks, Bar Nathansohn Levi, Irit Milman Krentsis, Einav Shoshan, Xiaohua Su, Maksim Mamonkin, Richard E Champlin, Yair Reisner, Esther Bachar Lustig

Faculty, Staff and Student Publications

Central memory CD8 T cells exhibit marked veto activity enhancing engraftment in several mouse models of T cell-depleted bone marrow (TDBM) allografting. Graft-versus-host disease (GVHD) can be prevented by stimulation of mouse or human memory CD8 T cells against their cognate antigens under cytokine deprivation, in the early phase of culture followed by further expansion with IL21, IL15, and IL7. Thus, human anti-viral CD8 central memory veto T cells generated from CMV and EBV-positive donors are currently evaluated in a clinical trial at MD Anderson Cancer Centre (MDACC). Results in 15 patients indicate a low risk of GVHD. Considering that …

Development Of A Novel Biomarker Platform For Profiling Key Protein-Protein Interactions To Predict The Efficacy Of Bh3-Mimetic Drugs, Andrew J Kinloch, Faiyaz Rahman, Bahriye Karakas, Muhammad Shahid, Bora Lim, Stephanie J Bouley, James A Walker, Erinna F Lee, Walter D Fairlie, Kevin R Kelly, Michael H Cardone

Faculty, Staff and Student Publications

One of the hallmarks of cancer cells is their failure to respond to the cellular mechanism of apoptosis. The B-cell lymphoma 2 (BCL-2) family of proteins regulate apoptosis. Their ability to do so can be measured using several methods that in turn anticipate the fate of the cancer cell in response to apoptosis-inducing treatment. These assays ultimately identify the readiness of the cancer cell to undergo apoptosis, which is referred to as the mitochondrial priming state. These metrics, however, have been challenging to implement in the clinic.

Multicenter Evaluation Of A New Strip-Based Blood Glucose System For Point-Of-Care Testing In Critical And Non-Critical Care Settings, Michael Goodman, Sven Bercker, Nancy Breitenbeck, Cristina Canada-Vilalta, Daisy D Canepa, William A Clarke, Christopher W Farnsworth, Edward O Ganser, Nienke Geerts, Barbara Goldsmith, Gary Headden, Debra Hoppensteadt, Birgit Klapperich, Ryan Matika, Gabrielle Miles, Sagori Mukhopadhyay, James H Nichols, Rebecca M O'Dell, Zubaid Rafique, Andre Schuetzenmeister, Robbert Slingerland, Ann F Stankiewicz, Jonathan R Swanson, Nam K Tran, Alan H B Wu, Brad S Karon

Faculty, Staff and Students Publications

Background: Evaluation of the performance of Cobas® Pulse (Roche Diagnostics GmbH, Mannheim, Germany), a new blood glucose (BG) monitoring system (BGMS; referred to here as BGMSA) intended for point-of-care testing using samples from patients in diverse clinical settings by intended point-of-care test operators.

Methods: Arterial, capillary, venous, or heel stick whole blood (WB) samples from patients in non-critical and critical care settings were collected and analyzed using BGMSA and the Nova StatStrip® BGMS (Nova Biomedical, Waltham, MA; referred to here as BGMSB), and a hexokinase comparator (Cobas 6000 Analyzer Series; Roche Diagnostics GmbH). The blood glucose measurement accuracy was assessed …

Neovascular Pruning By Ido1 Inhibitors Can Potentiate Immunogenic Cytotoxicity Of Ischemia-Targeted Agents To Synergistically Enhance Anti-Pd-1 Responsiveness, Shih-Chun Shen, Souvik Dey, James B. Duhadaway, Erika Sutanto-Ward, Maurice T. Hampton, Serguei V. Kozlov, George C. Prendergast, Alexander J. Muller

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Strategies for deploying indoleamine 2,3-dioxygenase 1 (IDO1)-targeted therapies for use against cancer have focused on IDO1's role in promoting peripheral immune tolerance that shields tumors from effector T cells. However, preclinical investigation of both primary and metastatic tumor development in the lungs has uncovered a previously unappreciated role for IDO1 in directing a counterregulatory response to interferon (IFN)-γ that realigns the local inflammatory environment to promote tumor neovascularization. Understanding how to therapeutically leverage the ability of IDO1 inhibitors to subvert inflammatory neovascularization within the tumor microenvironment has potential ramifications for future clinical development of these compounds.

METHODS: Pulmonary metastases …

The Tweak/Fn14 Signaling Mediates Skeletal Muscle Wasting During Cancer Cachexia, Meiricris Tomaz Da Silva, Anirban Roy, Anh Tuan Vuong, Aniket S Joshi, Cristeena Josphien, Meghana V Trivedi, Sajedah M Hindi, Vihang A Narkar, Ashok Kumar

Faculty, Staff and Student Publications

Cancer cachexia is a multifactorial syndrome characterized by progressive skeletal muscle wasting. The TWEAK-Fn14 system regulates muscle mass in diverse conditions. However, its role in the regulation of muscle mass during cancer cachexia remains less understood. Here, we demonstrate that the levels of Fn14 are induced in skeletal muscle of multiple mouse models of cancer cachexia. Muscle-specific deletion of Fn14 reduces myofiber atrophy in mouse models of pancreatic and lung cancer cachexia. Silencing of Fn14 in KPC pancreatic cancer cells prior to their implantation in mice attenuates tumor growth without affecting myofiber size. Muscle-specific deletion of Fn14 reduces the gene …

Secreted Phosphoprotein 1 In Lung Diseases, Hongli Liu, Cristian Coarfa, Arzoo N Charania, Jennifer L Larson-Casey, Ivan O Rosas, Chao He

Faculty, Staff and Students Publications

Secreted phosphoprotein 1 (SPP1), also known as osteopontin (OPN) or early T lymphocyte activation protein 1 (ETA-1), is a multifunctional protein involved in numerous biological processes, including immune modulation, stress response, and tissue remodeling. The role of SPP1 in interstitial lung diseases (ILDs) has become an area of increasing interest, given its elevated expression in various ILDs such as idiopathic pulmonary fibrosis (IPF), connective tissue disease-associated ILD (CTD-ILD), and pneumoconiosis, especially with recent data derived from single-cell RNA sequencing. In addition to ILDs, SPP1 has been implicated in infectious granulomatous lung diseases, lung and pleural malignancies, airway diseases, and COVID-19. …

Maternal Vitamin C Deficiency And Genetic Risk Factors Contribute To Congenital Defects Through Dysregulation Of Dna Methylation, Bernard K Van Der Veer, Colin Custers, Wannes Brangers, Riet Cornelis, Spyridon Champeris Tsaniras, Kobe De Ridder, Bernard Thienpont, Huiyong Cheng, Qiuying Chen, Daniel Kraushaar, Richard H Finnell, Steven S Gross, Kian Peng Koh

Faculty, Staff and Students Publications

Maternal dietary insufficiencies can reshape the fetal epigenome during gestation, contributing to birth defects and developmental disorders. Vitamin C (VitC) is a critical co-factor for Ten-Eleven-Translocation (TET) DNA demethylases, but the impact of its deficiency on embryonic development has gone largely unappreciated. Here, we show that maternal VitC deficiency in L-gulonolactone oxidase (Gulo)-deficient mice, which like humans are unable to synthesize VitC, can cause highly penetrant developmental delays and malformations in non-inbred embryos during the vulnerable period of gastrulation. DNA hypermethylation in Gulo−/− embryonic neural tissues of susceptible strains increases with VitC dose reduction and with the …

From Checkboxes To Emojis: A Novel Approach To Patient-Reported Outcomes In Multiple Sclerosis, Nur Neyal, Katelynn J Krey, Holly A Morrison, Nabeela Nathoo, Elizabeth J Atkinson, Jiye Son, Eoin P Flanagan, Sean J Pittock, Ugur Uygunoglu, Orhun H Kantarci, Burcu Zeydan

Faculty, Staff and Students Publications

Background: Patient-reported outcome measures (PROMs) improve multiple sclerosis (MS) management by reflecting patients' perspectives of their disease. Mayo Clinic Electronic Emoji Based Neurological Impairment Status (MEBNIS) is a short PROM consisting of four equally-weighted domains (MemoryMEBNIS, MoodMEBNIS, Fatigue-SleepinessMEBNIS, and AmbulationMEBNIS) and CompositeMEBNIS, which are based on emojis.

Objective: To investigate the correlations of MEBNIS with patient-reported, examination-based, performance-based, and radiological metrics of disease severity in persons with MS (pwMS).

Methods: PwMS (n = 195) prospectively completed MEBNIS, Expanded Disability Status Scale (EDSS), MS Functional Composite (MSFC) and its subtests [25-Foot Walk Test (25FWT), 9-Hole Peg Test (9HPT), Paced Auditory Serial …

Russell’S Viper Envenomation: The Challenge Of Diagnosis, Jing-Hua Lin, Wang-Chou Sung, Jiunn-Wang Liao, Dong-Zong Hung

BioMedicine

Russell’s viper envenomation is rare in Taiwan, and its typical clinical presentations, including consumption coagulopathy, acute renal failure, haemolysis, and increased capillary permeability, have been reported in the literature as case reports or series. Here, we report a case with an atypical presentation, and suspected to be a Russell’s viper bite due to the distinct characteristics of the snake and some progressive clinical signs/symptoms. He returned to health successfully after the correct antivenom was administered, and envenomation was ultimately confirmed by venom detection in the patient’s serum and urine samples.

Neurenteric Cysts: A Neurosurgical Case Series And Treatment Perspectives, Defran Ercan, Walter Stummer, Maryam Khaleghi Ghadiri

BioMedicine

Neurenteric cysts (NC) are rare lesions of endodermal origin lined by mucin-secreting cuboidal or columnar epithelium of an intestinal or respiratory type. They occur more frequently spinally than cranially. From the radiological view, NC may be confused with other lesions of the central nervous system, like arachnoid or epidermoid cysts. However, due to advances in neuroimaging, there is an increasing trend in preoperative diagnosis of NC. We are reporting three cases of NC, each exhibiting markedly distinct symptoms and postoperative courses. The first patient, a 45year-old woman, had NC in the fourth ventricle. Although she underwent surgery, the lesion recurred …

A Staged-Olif Approach Can Minimize Construct Lengths In Adult Spinal Deformity- A Case Series And Literature Review, Guna Pratheep Kalanchiama, Alexander Shao-Rong Pang, Jacob Yoong-Leong Oh

BioMedicine

Background:

Adult Spinal Deformity (ASD) is one of the challenging conditions to treat for spine surgeons. One of the important dilemmas in the management of these patients is the decision on the number of levels of instrumentation and the overall length of the construct. OLIF has the advantage of providing a minimally invasive approach to address this complex pathology also allowing us to stage the procedure and thus help clinicians reassess if the patient requires an additional decompression, long fusion lengths, or need for osteotomies.

Aim:

Our study aims to evaluate the possibility of minimizing the construct length following a …

Cyclohexylamine, The Principal Metabolite Of Cyclamate, Contracts The Epididymal Vas Deferens Of Rats By Affecting Endogenous Catecholamine Release Via Postsynaptic Α1aand Presynaptic Α2-Adrenoceptors In A Calcium-Dependent Manner, Yuh-Fung Chen, Yu-Wen Wang, Huei-Yann Tsai

BioMedicine

Background: Cyclohexylamine (CHA) is a principal metabolite of cyclamate, which was once one of the most prominently consumed non-sugar sweeteners. Earlier studies suggested that long-term use of cyclamate might be carcinogenic and genotoxic; however, no consistent evidence supports an association between cyclamate and cancer risk. However, this issue remains interesting. Cyclamate can be metabolized to CHA by the intestinal bacteria in humans and some animals. Previous reports indicated CHA could induce atrophy of rat testes and affect rat fertility, as well as contract rat vas deferens. However, the contractile mechanisms of CHA on rat vas deferens remains poorly understood. This …

Nutraceutical Benefits And Neuro-Protective Potent Of Four Colored Peppers (Capsicum Annuum Var. Grossum), Ya-Chen Yang, Chih-Lung Lin, Mei-Chin Yin

BioMedicine

Background: Four colored peppers (Capsicum annuum var. grossum), orange, purple, yellow and red, are plant foods served as salad or stir-fry for meals in Taiwan and many countries.

Purpose: This study aimed to investigate the multiple nutraceutical properties of aqueous extracts prepared from colored peppers.

Methods: Vitamin C content and phytochemical profiles of these peppers were analyzed. In vitro effects of anti-oxidative, anti-a-amylase, anti-a-glucosidase, antilipase and anti-acetylcholinesterase (AchE) of pepper aqueous extracts at 0.25, 0.5 and 1 mg were evaluated. The neuronal protective potent of pepper aqueous extracts at 0.5 and 1 mg in high glucose treated nerve growth factor …

The Protective Role Of Astaxanthin Against Oxidative Stress And Inflammation In Peritoneal Dialysis Rats, Ratih Tri Kusuma Dewi, Bambang Purwanto, Brian Wasita, Vitri Widyaningsih

BioMedicine

Background: Prolonged exposure of peritoneal membrane to dialysate solution is known to cause fibrosis mediated by imbalanced inflammatory response and oxidative stress. In this context, proinflammatory cytokines including TGF-β and IL-1β, along with oxidative stress markers namely SOD and MDA, present in circulation, could serve as indicators of fibrosis. This phenomenon has the potential to interfere with the optimization of Chronic Kidney Disease (CKD) treatment. Other oral antioxidant supplements have been widely studied to prevent peritoneal damage, but investigations regarding Astaxanthin (AST) effect on fibrosis marked with proinflammatory cytokine are still limited.

Aims: This study aimed to investigate the protective …

Benchmarking Machine Learning Models In Lesion-Symptom Mapping For Predicting Language Outcomes In Stroke Survivors, Deepa Tilwani, Christian O'Reilly, Nicholas Riccardi, Valerie L. Shalin, Dirk B. Den Ouden, Julius Fridriksson, Svetlana V. Shinkareva, Amit P. Sheth, Rutvik H. Desai

Communication Sciences and Disorders Faculty Articles and Research

Several decades of research have investigated the neural connections between stroke-induced brain damage and language difficulties. Typically, lesion-symptom mapping (LSM) studies that address this connection have relied on mass univariate statistics, which do not account for multidimensional relationships between variables. Machine learning (ML) techniques, which can capture these intricate connections, offer a promising complement to LSM methods. To test this promise, we benchmarked ML models on structural and functional MRI to predict aphasia severity (N = 238) and naming impairment (N = 191) for a cohort of chronic-stage stroke survivors. We used nested cross-validation to examine performance along …

Knowledge Discovery In Databases Of Proteomics By Systems Modeling In Translational Research On Pancreatic Cancer, Mathilde Resell, Elisabeth Pimpisa Graarud, Hanne-Line Rabben, Animesh Sharma, Lars Hagen, Linh Hoang, Nan T. Skogaker, Anne Aarvik, Magnus K. Svensson, Manoj Amrutkar, Caroline S. Verbeke, Surinder K. Batra, Gunnar Qvigstad, Timothy C. Wang, Anil Rustgi, Duan Chen, Chun-Mei Zhao

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Knowledge discovery in databases (KDD) can contribute to translational research, also known as translational medicine, by bridging the gap between

METHODS: This framework includes the data collection of a composition model (various research models), processing model (proteomics) and analytical model (bioinformatics, artificial intelligence/machine leaning and pattern evaluation), knowledge presentation, and feedback loops for hypothesis generation and validation. We applied this workflow to study pancreatic ductal adenocarcinoma (PDAC).

RESULTS: We identified the common proteins between human PDAC and various research models

CONCLUSIONS: This systems modeling workflow can be a valuable method for KDD, facilitating knowledge discovery in translational targets in …

Long-Term Neurocognitive And Behavioral Outcomes In Survivors Of Pediatric Brain Tumors: A Systematic Review, Tirath Patel, Pulkit Johar, Vaishnavi Kanisetti, Megan Szobody, Tori Sayers, Sriya Gullapalli, Murali Yallapu, Mushfiq Hassan Shaikh, Nikhilesh Anand, Kelsey Baker, Bharathi Gadad

School of Medicine Publications

Background: Brain tumors are among the most common neoplasms in children. These patients suffer from neurocognitive impairment, treatment-related side effects, and experience a subpar quality of life (QoL), affecting academic endeavors, social interaction, and mental wellbeing.

Methods: This review investigated different long-term neurocognitive and behavioral outcomes in pediatric brain tumor survivors and evaluated various effective treatment methods. We identified 75 relevant articles published between 2019 and 2024 using PubMed, PMC, Embase, and Google Scholar databases. Duplicates were removed, and 14 studies were finally selected following the PRISMA guidelines. Initial observations noted significant variations in the study methodologies and inclusion criteria. …

Biallelic Loss-Of-Function Variant In Minpp1 Causes Pontocerebellar Hypoplasia With Characteristic Severe Neurodevelopmental Disorder, Aljazi Al-Maraghi, Rulan Shaath, Katherine Ford, Waleed Aamer, Jehan Alrayahi, Sura Hussein, Elbay Aliyev, Nourhen Agrebi, Muhammad Kohailan, Satanay Z Hubrack, Sasirekha Palaniswamy, Adam D Kennedy, Karen L Debalsi, Sarah H Elsea, Ruba Benini, Tawfeg Ben-Omran, Bernice Lo, Ammira S A Akil, Khalid A Fakhro

Faculty, Staff and Students Publications

Pontocerebellar hypoplasia (PCH) encompasses a group of autosomal recessive neurodegenerative disorders marked by cerebellar and pontine atrophy. Multiple subtypes of PCH have been identified, among which the rare subtype PCH type 16 is caused by MINPP1 genetic variants. MINPPI encodes an enzyme essential for inositol polyphosphate dephosphorylation, regulating calcium and iron homeostasis. We conducted genome sequencing on a proband from the consanguineous family, who presented with a severe neurodegenerative disorder, to identify the underlying cause of disease. A comprehensive clinical assessment in addition to neuroradiological findings are described. We performed the functional validation of the identified variant and conducted untargeted …

Tavr In Older Adults With Cardiogenic Shock: Current Practice And Future Direction, Min Ji Kwak, Jorge A Irizarry-Caro, Paola Rodriguez Martinez, James Going, Jessica Lee, Dana Giza, Nuzah Amjad, Ana Leech, Rachel Jantea, Renee Flores, Nahid Rianon, Abhijeet Dhoble

Faculty, Staff and Student Publications

Aortic stenosis (AS) is one of the most common types of valvular heart disease in older adults, with age being significantly associated with the development of AS. The transcatheter aortic valve replacement (TAVR) procedure, since it was first performed in 2002, has emerged as a preferred treatment option for patients who are at intermediate to high surgical risk due to advanced age or medical comorbidities. Older adults with severe AS may present with acute decompensated heart failure leading to cardiogenic shock (CS). Among patients 65 years and older with AS presenting for TAVR, 4.1% were reportedly in acute CS. Regardless …

Comparison Of Thrombectomy Alone Versus Bridging Thrombolysis In A Us Population Using Regression Discontinuity Analysis, Youngran Kim, Sergio Salazar-Marioni, Rania Abdelkhaleq, Ananya Iyyangar, Diogo Haussen, Jonathan Grossberg, Jaydevsinh Dolia, Aqueel Pabaney, Mahmoud Mohammaden, Ameer Hassan, Wondwossen Tekle, Hamzah Saei, Mohamad Abdalkader, Piers Klein, Taha Nisar, Adeel Saleemi, Shahram Majidi, Johanna Fifi, Gabrielle Valestin, Guillermo Linares, Kara Christopher, David S Liebeskind, Mouhammad Jumaa, Syed Zaidi, Raul Nogueira, Brijesh Mehta, Joy Sessa, Juan Vivanco-Suarez, Aaron Rodriguez-Calienes, Milagros Galecio-Castillo, Santiago Ortega-Gutierrez, James Siegler, Mary Penckofer, Italo Linfante, Sunil A Sheth, Svin Registry Consortium

Faculty, Staff and Student Publications

The role of intravenous thrombolysis (IVT) in combination with endovascular thrombectomy (EVT) for the treatment of large vessel occlusion acute ischemic stroke has been evaluated exclusively outside the US, in randomized clinical trials which failed to demonstrate non-inferiority of skipping IVT. Because practice patterns and IVT dosing differ within the US, and prior observational US-based cohorts suggested improved clinical outcomes in patients who received IVT before EVT, a US-based evaluation is needed. This is a quasi-experimental study of a large US cohort using a regression discontinuity design (RDD) that enables the estimation of causal effects when randomization is not feasible. …

Methylation Risk Score Of C-Reactive Protein Associates Sleep Health With Related Health Outcomes, Ziqing Wang, Danielle A Wallace, Brian W Spitzer, Tianyi Huang, Kent D Taylor, Jerome I Rotter, Stephen S Rich, Peter Y Liu, Martha L Daviglus, Lifang Hou, Alberto R Ramos, Sonya Kaur, J Peter Durda, Hector M González, Myriam Fornage, Susan Redline, Carmen R Isasi, Tamar Sofer

Faculty, Staff and Student Publications

C-reactive protein (CRP) reflects inflammation status and is linked to poor sleep, metabolic and cardiovascular health. Methylation (MRS) and polygenic risk scores (PRS) reflect long-term systemic inflammation, and genetically-determined CRP, respectively. To refine understanding of inflammation-linked sleep and health outcomes, we construct PRS-CRPs using GWAS summary statistics and a previously-developed MRS-CRP in the Hispanic Community Health Study/Study of Latinos. Via survey-weighted linear regression, we estimate associations between blood-, PRS-, and MRS-CRP, with multiple sleep and health outcomes (n = 2217). MRS-CRP and PRS-CRPs are associated with increasing blood-CRP level by 43% and 23% per standard deviation. MRS-CRP is associated with …

Circulating Tumor Dna Monitoring And Blood Tumor Mutational Burden In Patients With Metastatic Solid Tumors Treated With Atezolizumab, Charles Swanton, Russell W Madison, Candice Francheska B Tambaoan, Funda Meric-Bernstam, Christopher J Sweeney, Razelle Kurzrock, Howard A Burris, David R Spigel, Hanna Tukachinsky, Jason Hughes, Julia Malato, Bongin Yoo, Tania Szado, Cheryl Schwab, Lincoln W Pasquina, Amaya Gasco, Katja Schulze, Claire F Friedman

Faculty, Staff and Student Publications

Immune checkpoint inhibitors are important for treatment across tumor types but are not universally effective in controlling disease. Early understanding of tumor response, or lack thereof, can inform treatment decisions. This study evaluates changes in circulating tumor DNA (ctDNA) and blood tumor mutational burden (bTMB) for associations with response to programmed cell death 1 ligand 1 (PD-L1) blockade. We sequenced cell-free DNA collected at the start of therapy, on treatment, and at the end of therapy for 153 patients treated with atezolizumab as part of the pan-tumor MyPathway study (NCT02091141). ctDNA tumor fraction (TF) and bTMB were assessed …

Nuclear Phase Separation Drives Npm1-Mutant Acute Myeloid Leukemia, Gandhar K Datar, Elmira Khabusheva, Archish Anand, Joshua Beale, Marwa Sadek, Chun-Wei Chen, Evdokiia Potolitsyna, Nayara Alcantara-Contessoto, Guangyuan Liu, Josephine De La Fuente, Christina Dollinger, Anna Guzman, Alejandra Martell, Katharina Wohlan, Abhishek Maiti, Nicholas J Short, S Stephen Yi, Vibeke Andresen, Bjørn Tore Gjertsen, Brunangelo Falini, Rachel E Rau, Lorenzo Brunetti, Nidhi Sahni, Margaret A Goodell, Joshua A Riback

Faculty, Staff and Students Publications

During cancer development, mutations promote gene expression changes that cause transformation. Leukemia is frequently associated with aberrant HOXA expression driven by translocations in nucleoporin genes or KMT2A, and mutations in NPM1. How disparate mutations converge on this regulatory pathway is not understood. Here we demonstrate that mutant NPM1 (NPM1c) forms nuclear condensates in multiple human cell lines, mouse models, and primary patient samples. We show NPM1c phase separation is necessary and sufficient to coordinate the recruitment of NUP98 and KMT2A to condensates. Through extensive mutagenesis and pharmacological destabilization of phase separation, we find that NPM1c condensates are necessary …