Low Cd25 In Alk+ Anaplastic Large Cell Lymphoma Is Associated With Older Age, Thrombocytopenia, And Increased Expression Of Surface Cd3 And Cd8, Shuyu E, L Jeffrey Medeiros, Hong Fang, Shaoying Li, Guilin Tang, Sa A Wang, Wei Wang, C Cameron Yin, M James You, Swaminathan P Iyer, Luis Malpica, Lianqun Qiu, Zhenya Tang, Qing Wei, Pei Lin, Jie Xu

Faculty, Staff and Student Publications

Background/objectives: Anaplastic lymphoma kinase (ALK)-positive (+) anaplastic large cell lymphoma (ALCL) is known to express CD25, but its significance has not been well studied.

Methods: In the present study, we identified 54 ALK+ ALCL patients with CD25 results available and investigated the significance of CD25 expression levels.

Results: Forty-two (78%) cases had high CD25 expressions, whereas low CD25 expressions were found in 12 (22%) cases. Compared with ALK+ ALCL patients with CD25-high neoplasms, patients with CD25-low neoplasms were older (median: 40 years vs. 29 years, p = 0.01) and more often had thrombocytopenia (40% vs. 0%, p = 0.02). Between …

Targeting Neuronal Nitric Oxide Synthase (Nnos) As A Novel Approach To Enhancing The Anti-Melanoma Activity Of Immune Checkpoint Inhibitors, Anika R. Patel, Shirley Tong, Kate Alison Lozada, Amardeep Awasthi, Richard B. Silverman, Jennifer Totonchy, Sun Yang

Pharmacy Faculty Articles and Research

Background and Objectives: Neuronal nitric oxide synthase (nNOS) overexpressed in melanoma plays a critical role in disease progression. Our previous studies demonstrated that nNOS inhibitors exhibited potent anti-melanoma activity and regulated PD-L1 expressions in the presence of interferon-gamma (IFN-γ). However, the role of nNOS in the melanoma immune response has not been well defined. Methods: Changes in gene expression profiles after nNOS inhibitor treatment were determined by transcriptomic analysis. A melanoma mouse model was used to determine the effects of nNOS inhibition on peripheral T cells and the in vivo anti-tumor activity of combining nNOS inhibitors with immune …

Implementation Of A Tracheostomy Discharge Education Class For Nicu Nurses, Todd N. Chamoy

Doctor of Nursing Practice Final Manuscripts

Infants who are ventilator-dependent or have anatomic anomalies of their airway frequently require tracheostomy placement prior to discharge from the hospital in order to be cared for safely at home. At this large quaternary children’s hospital in Southern California, preparing these infants for discharge after tracheostomy placement has not been the role of the NICU nurse. There was no system in place on how to train caregivers, and the NICU staff felt unprepared. Evidence supports use of intensive educational programs to improve nurse knowledge and skills of tracheostomy care, allowing NICU nurses to provide improved care and pre-discharge teaching.

A …

Implementing The Fib-4 Tool For Liver Fibrosis Screening In Diabetic Patients In Primary Care, Robert I. Montillano

Doctor of Nursing Practice Final Manuscripts

Abstract

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly non-non-alcoholic fatty liver disease (NAFLD), affects over 1 in 3 adults with type 2 diabetes mellitus (T2DM) and is a leading cause of advanced liver fibrosis. Despite guideline support from the American Diabetes Association (ADA) and American Association for the Study of Liver Diseases (AASLD), screening practices remain inconsistent in primary care. The Fibrosis-4 (FIB-4) index is a validated, low-cost, noninvasive tool for fibrosis risk stratification, yet it remains underutilized despite its availability in many electronic health record (EHR) systems.

Purpose: This Doctor of Nursing Practice (DNP) evidence-based practice (EBP) project …

Implementation Of A Health Care Transition Pathway For Children And Adults With Inborn Errors Of Metabolism: A Pilot Project, Brittany M. Murray

Doctor of Nursing Practice Scholarly Projects

Background: Children with medically complex diseases require highly specialized care by a highly specialized team. Those with rare disease, including inborn errors of metabolism (IEMs), are a medically complex population and face significant challenges undergoing the health care transition from a child/family-centered model to an adult/patient-centered model of care. The project site follows patients with IEMs in the Metabolism Program, but previously did not have a coordinated process and had insufficient resources for patients/families for the health care transition.

Methods: The Plan-Do-Study-Act (PDSA) method was utilized as the model for improvement. Due to the complexity of the population and time …

Cenobamate Use In Pregnancy: A Case Report, Tiara Paul, Maromi Nei

Department of Neurology Faculty Papers

No abstract provided.

“Non-Markovian” And “Directional” Errors Inhibit Scientific Self-Correction And Can Lead Fields Of Study Astray: An Illustration Using Gardening And Obesity-Related Outcomes, Jon Agley, Sarah E Deemer, David B Allison

Children’s Nutrition Research Center Staff Publications

Herein we coin the terms non-Markovian error and biased Markovian error to describe categories of scientific errors for which general progress within a field of study may be unlikely to result in scientific self-correction. We provide examples of such errors and show their impact on studies about gardening and obesity.

A Smart Pill Bottle And Text Messaging Intervention For Promoting Medication Adherence In Patients With Chronic Myeloid Leukemia: A Pilot Study Of Txt4 Tki, Kuang-Yi Wen, Neil Palmisiano, Rita Smith, Rachel Slamon, Gina Keiffer, Christian Fidler, Margaret Kasner, Lindsay Wilde, Md

Department of Medical Oncology Faculty Papers

BACKGROUND: Patients undergoing tyrosine kinase inhibitor (TKI) therapy for chronic myeloid leukemia (CML) often face challenges with adherence, despite the efficacy of the treatment. Theory-guided and evidence-informed interventions addressing psychosocial and adherence barriers are critical for promoting adherence. Using a mixed-method approach, the pilot study developed and evaluated the feasibility and potential impact of an intervention "txt4TKI," to support medication and symptom management among CML patients undergoing TKI therapy.

METHODS: Guided by the Necessity and Concerns framework, the study comprised two phases: Phase 1 involved qualitative patient needs assessment interviews informing intervention design. Phase 2 was a single-arm pilot study …

Thsd1 Is A Multifaceted Regulator In Health And Disease, Mengjun Dai, Kuizhi Qu, Sophie Liu, Zhen Xu, Yan-Ning Rui

Faculty, Staff and Student Publications

Thrombospondin Type 1 Domain-Containing Protein 1 (THSD1) is a transmembrane protein increasingly recognized for its critical roles in vascular biology and disease pathogenesis. Initially identified as a marker of hematopoietic stem and endothelial cells during embryogenesis, THSD1 has since been implicated in a wide spectrum of physiological and pathological processes. This paper consolidates current knowledge on THSD1, with a focus on its roles in vascular integrity, perinatal disorders, and tumorigenesis. In vascular systems, THSD1 promotes focal adhesion assembly and suppresses autophagy-mediated adhesion turnover, thereby stabilizing endothelial attachment and maintaining barrier function. Genetic and functional studies support its protective role against …

A Semiclassical Model Of The Immediate Temperature Distribution Surrounding The Track Of Heavy Ions With Therapeutic Energies, Martin Rädler, Niayesh Afshordi, Reza Taleei, Katia Parodi, Ramin Abolfath, Julie Lascaud

Department of Radiation Oncology Faculty Papers

Objective. Spikes of high temperature and pressure are created in the vicinity of heavy ions, especially at the Bragg peak. The expected subsequent thermoacoustic effects are however not well understood. In particular, the distribution of the densely packed primary interactions has not been considered in molecular dynamics (MDs) simulations or shock wave solutions. In this work, we derive a dedicated model to describe the primary interactions and their radial distribution, applicable to the modeling of acoustic and thermodynamic effects at the nanoscale. Approach. Starting from first principles, we assemble a semiclassical model of the energy loss of the primary heavy …

Self-Management For People With Epilepsy And A History Of Negative Health Events (Smart): A Randomized Controlled Effectiveness Trial, Martha Sajatovic, Jessica Black, Jacqueline Krehel-Montgomery, Richard Barigye, Joy Yala, Clara Adeniyi

Faculty Scholarship

Objectives: This 2-site, 6-month randomized controlled trial of an epilepsy self-management (ESM) curriculum (SMART) vs. 6-month waitlist (WL) control assessed effects on epilepsy outcomes in 160 people with epilepsy (PWE). Methods: PWE had at least 1 negative health event (NHE) defined as a seizure, emergency department visit, hospitalization or self-harm attempt in the last 6 months. Primary outcomes were differences in proportions of PWE with reductions in NHEs from baseline to 6 months follow up and change in NHE/seizure counts between SMART and WL. Secondary outcomes included the Patient Health Questionnaire (PHQ-9), 36-Item Short Form Survey (SF-36), Quality of Life …

A Hierarchy Of Pdz Domain Scaffolding Proteins Clusters The Kv1 K+ Channel Protein Complex At The Axon Initial Segment, Wei Zhang, Victoria L Palfini, Yu Wu, Xiaoyun Ding, Allison J Melton, Yudong Gao, Yuki Ogawa, Matthew N Rasband

Faculty, Staff and Students Publications

Action potentials are initiated and modulated at the axon initial segment (AIS) by highly clustered ion channels. Voltage-gated Kv1 potassium channels underlie most outward AIS K+ current. AIS Kv1 channels exist in a large protein complex including ADAM22, Caspr2, and LGI1. However, their clustering mechanisms remain unknown. Because Kv1 channels have a highly conserved PDZ-binding motif, we used CRISPR-based genome editing to screen 18 PDZ domain-containing proteins identified in our previous AIS proximity proteome for their AIS localization. Among these, we found that the scaffolding proteins SCRIB and PSD93 are highly enriched at the AIS. Using CRISPR-mediated knockout, cell surface …

Development And Pilot Testing Of An Addiction Clinic-Based Pre-Exposure Prophylaxis Uptake And Adherence Intervention For Women With Substance Use Disorders: Protocol For A Pilot Randomized Trial, Angela M Heads, Diane Santa Maria, Mandy J Hill, Robert Suchting, Kimberly N Evans, Zaneta Gaul, Luba Yammine, Constanza De Dios, Joy M Schmitz

Faculty, Staff and Student Publications

Background: Black and Hispanic women in the United States continue to bear disproportionate incidence of HIV related to sexual transmission and injection drug use. Specifically, women with substance use disorders (SUDs) are more likely to engage in vaginal or anal condomless sex associated with HIV transmission. Pre-exposure prophylaxis (PrEP) is a highly effective HIV prevention tool but is not widely used by racial or ethnic minority women. Effective interventions for engaging women with SUDs in HIV prevention interventions that are culturally appropriate and, therefore, more appealing to racial or ethnic minority women with SUDs are critically needed.

Objective: This 3-phased …

The Effect Of Celecoxib And Mumab911 On Strain Adaptive Bone Remodeling And Fracture Repair In Female Mice: Implications For Rapidly Progressive Osteoarthritis, Nicholas Ruggiero, Alexandra Ciuciu, Ashkan Sedigh, Ibtesam Rajpar, David Shelton, Patrice Belanger, Kathryn Gropp, John A. Collins, Theresa A. Freeman, Ryan E. Tomlinson

Department of Orthopaedic Surgery Faculty Papers

Debilitating pain is the primary clinical feature of osteoarthritis (OA) that drives the enormous healthcare costs. Osteoarthritis-related pain is often treated with non-steroidal anti-inflammatory drugs (NSAIDs), which effectively relieve pain and inflammation by inhibition of prostaglandin synthesis. Antibodies directed against nerve growth factor (NGF) were tested some time ago as an alternative potential analgesic for musculoskeletal pain, including osteoarthritis-related pain. Unfortunately, clinical development of these drugs was put on hold due to adverse outcomes - primarily rapidly progressive osteoarthritis. Both prostaglandin synthesis and NGF have been implicated as critical mediators of strain adaptive bone remodeling, which may play a role …

Cultivating Workplace Wellness: An Evaluation Of Gratitude Card Interventions Among University Faculty, Jeffrey Druck, Patrick Ockerse, Jamal Jones

Journal of Wellness

Introduction: There has been a growing interest in understanding the role of gratitude in promoting well-being. Gratitude, defined as a feeling of thankfulness and appreciation in response to receiving a benefit from someone else, has been shown to improve mood, increase social support, and decrease symptoms of depression and anxiety. This research paper explores an innovative intervention using gratitude cards for faculty members and measures the emotional impact of this intervention.

Methods: The study involved 32 clinical physicians from the Department of Emergency Medicine at the University of Utah. Participants were invited to write a gratitude card to …

Personalizing Neoadjuvant Chemotherapy Regimens For Triple-Negative Breast Cancer Using A Biology-Based Digital Twin, Chase Christenson, Chengyue Wu, David A Hormuth, Jingfei Ma, Clinton Yam, Gaiane M Rauch, Thomas E Yankeelov

Faculty, Staff and Student Publications

Despite advances triple negative breast cancer treatment, ~50% of patients will not achieve a pathological complete response prior to surgery with standard of care neoadjuvant therapy (NAT). We hypothesize that personalized regimens for NAT could significantly improve patient outcomes, which we address with a patient-specific digital twin framework. This framework is established by calibrating a biology-based model to longitudinal magnetic resonance images with approximate Bayesian computation. We then apply optimal control theory to either (1) reduce the final tumor cell number with equivalent dose, or (2) reduce the total dose of NAT with equivalent response. For (1), the personalized regimens …

Vegf In Diabetic Retinopathy And Age-Related Macular Degeneration, Andrew Callan, Justin Z. Heckman, Giani Tah, Samantha Lopez, Laura Valdez, Andrew Tsin

School of Medicine Publications

Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis throughout the human body, influencing countless physiological and pathological processes, including tumor growth, preeclampsia, and retinal diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). In DR, VEGF promotes retinal neovascularization and intraretinal fluid accumulation, leading to complications like diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR). Regular intravitreal anti-VEGF injections are commonly used to manage PDR and DME, though repeated treatments are often required, and efficacy can be limited. AMD, a major cause of vision loss in older adults, is characterized by either dry or …

Neuroanatomical And Morphometric Differences In Children Who Stutter, Mohammad A. Khan

Honors Scholar Theses

Childhood-Onset Fluency Disorder commonly known as stuttering is a neurodevelopmental speech disorder characterized by disruptions in speech fluency. While genetic and neurobiological factors are implicated, the structural brain differences underlying stuttering remain unclear. This study investigated neuroanatomical alterations in children who stutter (CWS) compared to typically fluent children (TFC), focusing on gray matter volume, cortical thickness, and surface area in speech-related regions; the Inferior Frontal Gyrus, Middle Temporal Gyrus, and Pre-motor Operculum. High-resolution MRI data from 100 children (48 CWS, 52 TFC) aged 3–12 years were analyzed using FreeSurfer. Group comparisons revealed no statistically significant differences in cortical thickness, surface …

Renal Denervation Improves Cardiac Function And Exercise Duration In A Miniswine Model Of Heart Failure With Preserved Ejection Fraction, David J. Lefer, Thomas E. Sharp, Amy L. Scarborough, Amelia G. Haydel, Sanjiv J. Shah, Zhen Li, Traci T. Goodchild

School of Medicine Faculty Publications

Aims: Overactivity of the sympathetic nervous system is a common underlying mechanism in development and progression of several heart failure with preserved ejection fraction (HFpEF) comorbidities. Decreasing renal sympathetic nerve activity using catheter-based renal denervation (RDN) systems have shown efficacy in treating resistant hypertension and cardiac dysfunction in heart failure with reduced ejection fraction. The purpose of this study was to determine if modulation of renal sympathetic nerve activity by RDN improves cardiac function and exercise tolerance in a clinically-relevant minipig model of cardiometabolic HFpEF. Methods and results: Multiple HFpEF comorbidities were induced in adult female Göttingen minipigs by mineralocorticoid …

Mental Health And The Role Of Social Support In The Lives Of Vulnerabilized Sexual Minority Women, Jennifer L. Glick, Megan G. Nguyen, Aimee K. Huang, Kamila A. Alexander, Danielle German

School of Public Health Faculty Publications

Introduction Sexual minority women (SMW; women who self-identify as lesbian, queer, etc., as well as heterosexually-identified women who experience attraction to romantic or sexual partnerships with women) and vulnerabilized women (those marginalized due to structural forces such as housing insecurity, violence, sex exchange, drug use, or HIV positive status) experience a range of mental health challenges compared to their heterosexual and general population counterparts. General populations studies show a positive relationship between social support and mental health; less is known about SMW experiencing intersecting multi-layered vulnerabilities. This study characterizes mental health stressors, identifies social support sources and forms, and explores …

Untargeted Proteomics Enables Ultra-Rapid Variant Prioritisation In Mitochondrial And Other Rare Diseases, Daniella H Hock, Nikeisha J Caruana, Liana N Semcesen, Nicole J Lake, Luke E Formosa, Sumudu S C Amarasekera, Tegan Stait, Simone Tregoning, Leah E Frajman, Adam M Bournazos, David R L Robinson, Megan Ball, Boris Reljic, Bryony Ryder, Mathew J Wallis, Anand Vasudevan, Cara Beck, Heidi Peters, Joy Lee, Natalie B Tan, Mary-Louise Freckmann, Mitomdt Diagnostic Network For Genomics And Omics, Vasiliki Karlaftis, Chantal Attard, Paul Monagle, Amanda Samarasinghe, Rosie Brown, Weimin Bi, Monkol Lek, Robert Mcfarland, Robert W Taylor, Michael T Ryan, Sandra T Cooper, Zornitza Stark, John Christodoulou, Alison G Compton, David R Thorburn, David A Stroud

Faculty, Staff and Students Publications

Background: Only half of individuals with suspected rare diseases receive a genetic diagnosis following genomic testing. A genetic diagnosis allows access to appropriate care, restores reproductive confidence and reduces the number of potentially unnecessary interventions. A major barrier is the lack of disease agnostic functional tests suitable for implementation in routine diagnostics that can provide evidence supporting pathogenicity of novel variants, especially those refractory to RNA sequencing.

Methods: Focusing on mitochondrial disease, we describe an untargeted mass-spectrometry based proteomics pipeline that can quantify proteins encoded by > 50% of Mendelian disease genes and > 80% of known mitochondrial disease genes in clinically …

Multicomponent Parenteral Lipid Emulsions Do Not Prevent Liver Injury In Neonatal Pigs With Obstructive Cholestasis, Greg Guthrie, Caitlin Vonderohe, Valeria Meléndez Hebib, Barbara Stoll, Douglas Burrin

Children’s Nutrition Research Center Staff Publications

Biliary atresia (BA) is a pediatric liver disease that often necessitates parenteral nutrition (PN) to support growth due to impaired liver function. While soy-based lipid emulsions (SLE) are commonly used in PN, they may contribute to cholestatic liver injury. In contrast, mixed lipid emulsions (MLE) show promise in preventing cholestasis in infants without BA, potentially by restoring bile flow. However, their effectiveness in patients of complete bile duct obstruction, as seen in BA, remains uncertain. To explore the potential benefits of MLE in BA, we utilized a neonatal pig model of bile duct ligation (BDL). Pigs underwent either BDL or …

The Joint Association Of Diet Quality And Sleep Regularity With Incident Cardiovascular Disease In The Multi-Ethnic Study Of Atherosclerosis, Kaitlin S Potts, Claire Veldkamp, Alexis C Wood, Erin D Michos, Raymond Noordam, Tianyi Huang, Susan Redline, Heming Wang

Children’s Nutrition Research Center Staff Publications

Background/objectives: Diet quality and sleep regularity both influence cardiovascular disease (CVD) risk and may influence each other, but there is scarce evidence for their joint or interacting associations in relation to CVD. We assessed these associations in the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods: Participants free of CVD with valid diet and sleep measures in 2010-2013 were included and followed through 2020 for detection of incident CVD (188 events detected over 8.8 years among 1782 participants; 55% women). Sleep timing and duration regularity were assessed via the intra-individual SD of sleep onset time and duration across 5- to 7-day actigraphy. …

Post-Recovery Viral Shedding Shapes Wastewater-Based Epidemiological Inferences, Tin Phan, Samantha Brozak, Bruce Pell, Stanca M Ciupe, Ruian Ke, Ruy M Ribeiro, Anna Gitter, Kristina D Mena, Alan S Perelson, Yang Kuang, Fuqing Wu

Faculty, Staff and Student Publications

Background: The prolonged viral shedding from the gastrointestinal tract is well documented for numerous pathogens, including SARS-CoV-2. However, the impact of prolonged viral shedding on epidemiological inferences using wastewater data is not yet fully understood.

Methods: To gain a better understanding of this phenomenon at the population level, we extended a wastewater-based modeling framework that integrates viral shedding dynamics, viral load data in wastewater, case report data, and an epidemic model.

Results: Our results indicate that as an outbreak progresses, the viral load from recovered individuals gradually becomes predominant, surpassing that from the infectious population. This phenomenon leads to a …

Commencement, Philadelphia (2025), Philadelphia College Of Osteopathic Medicine

Commencements

Philadelphia Campus Commencement Program, 2025. Degrees include Doctor of Osteopathic Medicine, Doctor of Philosophy in Educational Psychology, Doctor of Psychology in Clinical Psychology, Doctor of Psychology in School Psychology, Educational Specialist in School Psychology, Master of Science in Applied Behavioral Analysis, Master of Science in Applied Positive Psychology, Master of Science in Mental Health Counseling, Master of Science in Biomedical Sciences, Master of Science in Forensic Medicine, Master of Science in Health Sciences - Physician Assistant Studies.

Commencement Speaker: John J. Lynch III.

Decoding Resistance To Immune Checkpoint Inhibitors In Non-Small Cell Lung Cancer: A Comprehensive Analysis Of Plasma Proteomics And Therapeutic Implications, Michal Harel, Nili Dahan, Coren Lahav, Eyal Jacob, Yehonatan Elon, Igor Puzanov, Ronan J. Kelly, Yuval Shaked, Raya Leibowitz, David P. Carbone, David R. Gandara, Adam P. Dicker

Department of Radiation Oncology Faculty Papers

BACKGROUND: Immune checkpoint inhibitors (ICIs) have shown substantial benefit for patients with advanced non-small cell lung cancer (NSCLC). However, resistance to ICIs remains a major clinical challenge. Here, we perform a comprehensive bioinformatic analysis of plasma proteomic profiles to explore the underlying biology of treatment resistance in NSCLC.

METHODS: The analysis was performed on 388 "resistance-associated proteins" (RAPs) that were previously described as pretreatment plasma proteomic predictors within the PROphet computational model designed to predict ICI clinical benefit in NSCLC. Putative tissue origins of the RAPs were explored using publicly available datasets. Enrichment analyses were performed to investigate RAP-related biological …

Predicting Pathologic ≥N2 Disease In Women With Breast Cancer, Kerollos Nashat Wanis, Wenli Dong, Yu Shen, Funda Meric-Bernstam, Taiwo Adesoye, Henry M Kuerer, Abigail S Caudle, Nina Tamirisa, Sarah M Desnyder, Susie X Sun, Isabelle Bedrosian, Puneet Singh, Solange E Cox, Kelly K Hunt, Rosa F Hwang

Faculty, Staff and Student Publications

The distinction between pN1 and ≥pN2 breast cancer impacts treatment decisions. Using data from a single institution on women with cN0 invasive breast cancer who were treated with upfront surgery, had 1-3 positive SLNs, and underwent completion ALND, we used gradient boosted trees (XGBoost) to develop a model for predicting ≥pN2 disease using clinicopathologic variables. Model performance was tested in a held-out subsample (20%) and validated using data from the National Cancer Database (NCDB). Of 3574 patients with cN0 breast cancer, 587 underwent upfront surgery and had 1-3 positive SLNs. Of these, 415 (70.7%) underwent completion ALND, with 64 (15.4%) …

Comprehensive Evaluation Of Phosphoproteomic-Based Kinase Activity Inference, Sophia Müller-Dott, Eric J Jaehnig, Khoi Pham Munchic, Wen Jiang, Tomer M Yaron-Barir, Sara R Savage, Martin Garrido-Rodriguez, Jared L Johnson, Alessandro Lussana, Evangelia Petsalaki, Jonathan T Lei, Aurelien Dugourd, Karsten Krug, Lewis C Cantley, D R Mani, Bing Zhang, Julio Saez-Rodriguez

Faculty, Staff and Students Publications

Kinases regulate cellular processes and are essential for understanding cellular function and disease. To investigate the regulatory state of a kinase, numerous methods have been developed to infer kinase activities from phosphoproteomics data using kinase-substrate libraries. However, few phosphorylation sites can be attributed to an upstream kinase in these libraries, limiting the scope of kinase activity inference. Moreover, inferred activities vary across methods, necessitating evaluation for accurate interpretation. Here, we present benchmarKIN, an R package enabling comprehensive evaluation of kinase activity inference methods. Alongside classical perturbation experiments, benchmarKIN introduces a tumor-based benchmarking approach utilizing multi-omics data to identify highly active …

The Perk/Atf4 Pathway Is Required For Metabolic Reprogramming And Progressive Lung Fibrosis, Jyotsana Pandey, Jennifer L Larson-Casey, Mallikarjun H Patil, Chao He, Nisarat Pinthong, A Brent Carter

Faculty, Staff and Students Publications

Asbestosis is a prototypical type of fibrosis that is progressive and does not resolve. ER stress is increased in multiple cell types that contribute to fibrosis; however, the mechanism(s) by which ER stress in lung macrophages contributes to fibrosis is poorly understood. Here, we show that ER stress resulted in protein kinase RNA-like ER kinase (PERK; Eif2ak3) activation in humans with asbestosis. Similar results were seen in asbestos-injured mice. Mice harboring a conditional deletion of Eif2ak3 were protected from fibrosis. Lung macrophages from asbestosis individuals had evidence of metabolic reprogramming to fatty acid oxidation (FAO). Eif2ak3fl/fl mice had increased oxygen …

Impact Of Transcatheter Aortic Valve Implantation (Tavi) On Left Ventricular Mass, Volumes, And Pressure. A Single-Center Echocardiographic Analysis, Fouad Taiwilaa Alshammari, Afrah Asaad Alonazi, Mohammed Dhaifallah Almutairi, Khaled Ahmed Majrashi, Atheer Mansour Almutairi, Muhammad Azam Shah

Journal of the Saudi Heart Association

Background: Transcatheter aortic valve implantation (TAVI) is an alternative treatment for surgically high-risk patients with severe aortic stenosis (AS). This study aimed to assess the echocardiographic outcomes of TAVI in patients with severe AS, focusing on left ventricular mass, volume, and pressure.

Methods: This retrospective,registry-based, single-center study was conducted at King Salman Heart Center, Riyadh, Saudi Arabia. We included 200 adult patients who underwent the TAVI procedure and completed at least one year of clinical and echocardiographic follow-up. Baseline demographic, clinical, and echocardiographic data were collected and paired pre- and post-procedure echocardiographic measurements were analyzed.

Result: Paired analysis …