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2023

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Full-Text Articles in Medical Specialties

Development Of An Equitable, Interprofessional Medical Cannabis Education, Certification And Research Program In An Nci-Designated Cancer Center, Gregory Garber, Msw, Jillian Van Sciver, Mba, Denise Young, Msw, Latrisha Bentch, Ba, Bracken Babula, Md, Brooke Worster, Md Mar 2023

Development Of An Equitable, Interprofessional Medical Cannabis Education, Certification And Research Program In An Nci-Designated Cancer Center, Gregory Garber, Msw, Jillian Van Sciver, Mba, Denise Young, Msw, Latrisha Bentch, Ba, Bracken Babula, Md, Brooke Worster, Md

Department of Medical Oncology Posters

Background: Medical cannabis (MC), state-regulated cannabis programs accessible with a physician certification for a qualifying diagnosis, now exist in 47 states. Little attention has been paid to ensuring equitable access to such programs for the most vulnerable cancer patients.1 Estimates of cannabis use in cancer patients range from 30-40%2 yet access to MC is highly dependent on a number of variables including: geography, cost, availability of certifying providers, lack of provider education and a confusing array of state programs coupled with ongoing federal illegality. The historic criminalization of cannabis and the disproportionate impact on People of Color creates another …


Assessing Risk Factors For 90-Day Emergency Department Visits Status-Post Index Total Knee Arthroplasty: A Retrospective Case Control Study, Ian Penvose, Helen E. Huetteman, Phil Vartanyan, James Feng, Robert Runner, Drew Douglas Moore, Mark S. Karadsheh Mar 2023

Assessing Risk Factors For 90-Day Emergency Department Visits Status-Post Index Total Knee Arthroplasty: A Retrospective Case Control Study, Ian Penvose, Helen E. Huetteman, Phil Vartanyan, James Feng, Robert Runner, Drew Douglas Moore, Mark S. Karadsheh

Conference Presentation Abstracts

INTRODUCTION: With the increasing adoption of value-based healthcare initiatives in total knee arthroplasty (TKA), a greater emphasis has been placed on implementing cost-saving measures while maintaining or improving quality of care. One area of interest has been postoperative ED visits. Here we evaluate potential risk factors for 90-day ED visits. METHODS: This is a case control study from a large, tertiary, private, academic institution. All primary TKAs between 7/1/2013 to 12/31/2017 were obtained retrospectively from a prospective institutional database utilized for contribution to a state-wide joint arthroplasty database. All patient charts were subsequently verified and reviewed for all-cause 90-day ED …


Emphysematous Pyelonephritis Necessitating Bilateral Radical Nephrectomy: A Case Report And Literature Review., Christine E Wamsley, Arianna Morton, Christopher G Roth, Joseph K Izes, Li Li Mar 2023

Emphysematous Pyelonephritis Necessitating Bilateral Radical Nephrectomy: A Case Report And Literature Review., Christine E Wamsley, Arianna Morton, Christopher G Roth, Joseph K Izes, Li Li

Computational Medicine Center Faculty Papers

Emphysematous pyelonephritis (EPN) is a severe, acute necrotizing infection of the kidney with gas accumulation in the renal parenchyma, collecting ducts, and/or perirenal tissue. We report a case of EPN in a 66 year-old male with uncontrolled diabetes mellitus (DM), urinary tract infection and septic shock necessitating emergent bilateral radical nephrectomy. Morphologically, the kidney parenchyma revealed severe acute bacterial pyelonephritis with extensive abscesses, gas cysts, necrosis and foci of infarctions. The uninvolved background cortex parenchyma exhibited diabetic nephropathy (DN), Class IIB. Post-operatively, the patient remained dialysis-dependent with multiple re-admissions for recurrent multi-drug resistant


Surgeon Estimations Of Acetabular Cup Orientation Using Intraoperative Fluoroscopic Imagining Are Unreliable., Parker L Brush, Adrian Santana, Gregory R Toci, Eric Slotkin, Michael Solomon, Tristan Jones, Arjun Saxena Mar 2023

Surgeon Estimations Of Acetabular Cup Orientation Using Intraoperative Fluoroscopic Imagining Are Unreliable., Parker L Brush, Adrian Santana, Gregory R Toci, Eric Slotkin, Michael Solomon, Tristan Jones, Arjun Saxena

Rothman Institute Papers

BACKGROUND: Accurate acetabular cup orientation is associated with decreased revision rates and improved outcomes of primary total hip arthroplasty. This study assesses surgeon's ability to estimate both the acetabular component inclination and anteversion angles via intraoperative fluoroscopy (IF) images.

METHODS: We surveyed orthopedic surgeons to estimate acetabular component inclination and anteversion based on 20 IF images of total hip arthroplasty through a direct anterior approach. Postoperative computed-tomography scans were used to calculate the true inclination and anteversion component angles. The absolute difference between the true and estimated values was calculated to determine the mean and standard deviation of the survey …


Variable Shift Lengths Negatively Affect Emergency Medicine Resident Wellness, Marcus Fazzari, Joseph Longobardi, Joseph Mccarthy, Matthew Hysell, Sidney Hann Mar 2023

Variable Shift Lengths Negatively Affect Emergency Medicine Resident Wellness, Marcus Fazzari, Joseph Longobardi, Joseph Mccarthy, Matthew Hysell, Sidney Hann

Journal of Wellness

Introduction: Burnout is very common in emergency medicine and there has been extensive research evaluating factors that contribute to burnout. We sought to examine the contributions of post-graduate year (PGY), shifts worked per month, patients seen per shift, and length of shifts to emergency medicine resident burnout.

Methods: All emergency medicine residents were surveyed with regards to their PGY, shifts worked per month, patients seen per shift, and length of shifts. They were administered the Stanford Wellness Survey and asked to globally rate their degree of burnout. We then modeled whether consideration of the surveyed factors increased the …


Moving Senolytics Closer To The Clinic In Ipf, Daniel Kramer, Gautam George, Ross Summer Mar 2023

Moving Senolytics Closer To The Clinic In Ipf, Daniel Kramer, Gautam George, Ross Summer

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

No abstract provided.


Preparation And Synergy Of Supported Ru0 And Pd0 For Rapid Chlorate Reduction At Ph 7, Jinyu Gao, Shaohua Xie, Fudong Liu, Jinyong Liu Mar 2023

Preparation And Synergy Of Supported Ru0 And Pd0 For Rapid Chlorate Reduction At Ph 7, Jinyu Gao, Shaohua Xie, Fudong Liu, Jinyong Liu

Faculty, Staff and Student Publications

Chlorate (ClO3–) is a common water pollutant due to its gigantic scale of production, wide applications in agriculture and industry, and formation as a toxic byproduct in various water treatment processes. This work reports on the facile preparation, mechanistic elucidation, and kinetic evaluation of a bimetallic catalyst for highly active ClO3– reduction into Cl–. Under 1 atm H2 and 20 °C, PdII and RuIII were sequentially adsorbed and reduced on a powdered activated carbon support, affording Ru0–Pd0/C from scratch within only 20 min. The Pd0 particles significantly accelerated the reductive immobilization of RuIII as >55% dispersed Ru0 outside Pd0. At …


Multifaceted Role For P53 In Pancreatic Cancer Suppression, Stephano S Mello, Brittany M Flowers, Pawel K Mazur, James J Lee, Fabian Müller, Sarah K Denny, Sofia Ferreira, Kathryn Hanson, Seung K Kim, William J Greenleaf, Laura D Wood, Laura D Attardi Mar 2023

Multifaceted Role For P53 In Pancreatic Cancer Suppression, Stephano S Mello, Brittany M Flowers, Pawel K Mazur, James J Lee, Fabian Müller, Sarah K Denny, Sofia Ferreira, Kathryn Hanson, Seung K Kim, William J Greenleaf, Laura D Wood, Laura D Attardi

Faculty, Staff and Student Publications

The vast majority of human pancreatic ductal adenocarcinomas (PDACs) harbor TP53 mutations, underscoring p53's critical role in PDAC suppression. PDAC can arise when pancreatic acinar cells undergo acinar-to-ductal metaplasia (ADM), giving rise to premalignant pancreatic intraepithelial neoplasias (PanINs), which finally progress to PDAC. The occurrence of TP53 mutations in late-stage PanINs has led to the idea that p53 acts to suppress malignant transformation of PanINs to PDAC. However, the cellular basis for p53 action during PDAC development has not been explored in detail. Here, we leverage a hyperactive p53 variant-p5353,54-which we previously showed is a more robust PDAC suppressor than …


Poor Seizure Control Among Children Attending A Tertiary Hospital In South Western Uganda – A Retrospective Study, Martha Sajatovic Mar 2023

Poor Seizure Control Among Children Attending A Tertiary Hospital In South Western Uganda – A Retrospective Study, Martha Sajatovic

Faculty Scholarship

Background: Seizure control among children with epilepsy (CWE) receiving anti-seizure medications (ASMs) remains a challenge in low-resource settings. Uncontrolled seizures are significantly associated with increased morbidity and mortality among CWE. This negatively impacts their quality of life and increases stigma. Aim: This study determined seizure control status and described the factors associated among CWE receiving ASMs at Mbarara Regional Referral Hospital (MRRH). Methods: In a retrospective chart review study, socio-demographic and clinical data were obtained from 112 medical records. CWE receiving ASMs for at least six months and regularly attending the clinic were included in the study. Physical or telephone …


A Comprehensive And Integrative Approach To Mecp2 Disease Transcriptomics, Alexander J Trostle, Lucian Li, Seon-Young Kim, Jiasheng Wang, Rami Al-Ouran, Hari Krishna Yalamanchili, Zhandong Liu, Ying-Wooi Wan Mar 2023

A Comprehensive And Integrative Approach To Mecp2 Disease Transcriptomics, Alexander J Trostle, Lucian Li, Seon-Young Kim, Jiasheng Wang, Rami Al-Ouran, Hari Krishna Yalamanchili, Zhandong Liu, Ying-Wooi Wan

Faculty, Staff and Students Publications

Mutations in MeCP2 result in a crippling neurological disease, but we lack a lucid picture of MeCP2's molecular role. Individual transcriptomic studies yield inconsistent differentially expressed genes. To overcome these issues, we demonstrate a methodology to analyze all modern public data. We obtained relevant raw public transcriptomic data from GEO and ENA, then homogeneously processed it (QC, alignment to reference, differential expression analysis). We present a web portal to interactively access the mouse data, and we discovered a commonly perturbed core set of genes that transcends the limitations of any individual study. We then found functionally distinct, consistently up- and …


A Case Of Congenital Coronary Sinus Ostial Atresia With Persistent Left Superior Vena Cava, Laura Onderko, Thomas A. Miller, Sean Novak, Jeffrey Rosenblatt Mar 2023

A Case Of Congenital Coronary Sinus Ostial Atresia With Persistent Left Superior Vena Cava, Laura Onderko, Thomas A. Miller, Sean Novak, Jeffrey Rosenblatt

Journal of Maine Medical Center

Introduction: The coronary sinus is responsible for venous drainage of the heart. Congenital anomalies of the coronary sinus are rare and typically associated with other anomalies, such as atrial septal defects or other congenital heart malformations.

Clinical Findings: We present a case of incidentally found atresia of the coronary sinus ostium with associated persistent left superior vena cava. This case involved a 52-year-old patient who initially presented with a supraventricular tachycardia and elevated troponin.

Clinical Course: The patient underwent cardiac workup with a coronary computed tomographic angiography scan. This scan showed no obstructive coronary artery disease, but did show congenital …


Understanding The Burden Of Traumatic Injuries At The United States-Mexico Border: A Scoping Review Of The Literature, Benjamin A. Keller, Jeffrey Skubic, Monica Michelle Betancourt-Garcia, Romeo C. Ignacio, Jason S. Radowsky, Alan H. Tyroch, Carlos Palacio Lascano, Bellal Joseph, Collin Stewart, Aaron Silva Mar 2023

Understanding The Burden Of Traumatic Injuries At The United States-Mexico Border: A Scoping Review Of The Literature, Benjamin A. Keller, Jeffrey Skubic, Monica Michelle Betancourt-Garcia, Romeo C. Ignacio, Jason S. Radowsky, Alan H. Tyroch, Carlos Palacio Lascano, Bellal Joseph, Collin Stewart, Aaron Silva

School of Medicine Publications

The United States-Mexico border is the busiest land crossing in the world and faces continuously increasing numbers of undocumented border crossers. Significant barriers to crossing are present in many regions of the border, including walls, bridges, rivers, canals, and the desert, each with unique features that can cause traumatic injury. The number of patients injured attempting to cross the border is also increasing, but significant knowledge gaps regarding these injuries and their impacts remain. The purpose of this scoping literature review is to describe the current state of trauma related to the US–Mexico border to draw attention to the problem, …


Risk Of Diabetic Retinopathy Between Sodium-Glucose Cotransporter-2 Inhibitors And Glucagon-Like Peptide-1 Receptor Agonists, Tzu-Yi Lin, Eugene Yu-Chuan Kang, Shih-Chieh Shao, Edward Chia-Cheng Lai, Sunir J. Garg, Kuan-Jen Chen, Je-Ho Kang, Wei-Chi Wu, Chi-Chun Lai, Yih-Shiou Hwang Mar 2023

Risk Of Diabetic Retinopathy Between Sodium-Glucose Cotransporter-2 Inhibitors And Glucagon-Like Peptide-1 Receptor Agonists, Tzu-Yi Lin, Eugene Yu-Chuan Kang, Shih-Chieh Shao, Edward Chia-Cheng Lai, Sunir J. Garg, Kuan-Jen Chen, Je-Ho Kang, Wei-Chi Wu, Chi-Chun Lai, Yih-Shiou Hwang

Wills Eye Hospital Papers

BACKGROUND: To compare risk of diabetic retinopathy (DR) between patients taking sodium-glucose cotransporter-2 inhibitors (SGLT2is) and those taking glucagon-like peptide-1 receptor agonists (GLP1-RAs) in routine care.

METHODS: This retrospective cohort study emulating a target trial included patient data from the multi-institutional Chang Gung Research Database in Taiwan. Totally, 33,021 patients with type 2 diabetes mellitus using SGLT2is and GLP1-RAs between 2016 and 2019 were identified. 3,249 patients were excluded due to missing demographics, age <40 >years, prior use of any study drug, a diagnosis of retinal disorders, a history of receiving vitreoretinal procedure, no baseline glycosylated hemoglobin, or no follow-up data. …


International Consensus Statement On Allergy And Rhinology: Allergic Rhinitis – 2023, Sarah K. Wise, Cecelia C. Damask, Lauren T. Roland, Charles Ebert, Joshua M. Levy, Sandra Lin, Amber Luong, Kenneth Rodriguez, Ahmad R. Sedaghat, Helene J. Krouse Mar 2023

International Consensus Statement On Allergy And Rhinology: Allergic Rhinitis – 2023, Sarah K. Wise, Cecelia C. Damask, Lauren T. Roland, Charles Ebert, Joshua M. Levy, Sandra Lin, Amber Luong, Kenneth Rodriguez, Ahmad R. Sedaghat, Helene J. Krouse

School of Medicine Publications

Background

In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR-Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR-Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated. The executive summary highlights key evidence-based findings and recommendation from the full document.

Methods

ICAR-Allergic Rhinitis 2023 employed established evidence-based review with recommendation (EBRR) methodology to individually evaluate each topic. Stepwise iterative peer review and consensus …


Immortalized B Cells Transfected With Mrna Of Antigen Fused To Mitd (Ibmam): An Effective Tool For Antigen-Specific T-Cell Expansion And Tcr Validation, Zhe Wang, Tiantian Zhang, Aaron Anderson, Vincent Lee, Szymon Szymura, Zhenyuan Dong, Benjamin Kuang, Elizabeth Oh, Jingwei Liu, Sattva S Neelapu, Larry Kwak, Soung-Chul Cha Mar 2023

Immortalized B Cells Transfected With Mrna Of Antigen Fused To Mitd (Ibmam): An Effective Tool For Antigen-Specific T-Cell Expansion And Tcr Validation, Zhe Wang, Tiantian Zhang, Aaron Anderson, Vincent Lee, Szymon Szymura, Zhenyuan Dong, Benjamin Kuang, Elizabeth Oh, Jingwei Liu, Sattva S Neelapu, Larry Kwak, Soung-Chul Cha

Faculty, Staff and Student Publications

Peripheral mononuclear blood cells (PBMCs) are the most widely used study materials for immunomonitoring and antigen-specific T-cell identification. However, limited patient PBMCs and low-frequency antigen-specific T cells remain as significant technical challenges. To address these limitations, we established a novel platform comprised of optimized HLA-matched immortalized B cells transfected with mRNA of a prototype viral or tumor antigen conjugated to MHC class-I trafficking domain protein (MITD) to increase the efficiency of epitope expression in antigen-presenting cells (APCs) essential to expanding antigen-specific T cells. When applied to CMV as a model, the IBMAM platform could successfully expand CMV-specific T cells from …


Phenotypic Plasticity In Circulating Tumor Cells Is Associated With Poor Response To Therapy In Metastatic Breast Cancer Patients, Evan N Cohen, Gitanjali Jayachandran, Hui Gao, Phillip Peabody, Heather B Mcbride, Franklin D Alvarez, Megumi Kai, Juhee Song, Yu Shen, Jie S Willey, Bora Lim, Vicente Valero, Naoto T Ueno, James M Reuben Mar 2023

Phenotypic Plasticity In Circulating Tumor Cells Is Associated With Poor Response To Therapy In Metastatic Breast Cancer Patients, Evan N Cohen, Gitanjali Jayachandran, Hui Gao, Phillip Peabody, Heather B Mcbride, Franklin D Alvarez, Megumi Kai, Juhee Song, Yu Shen, Jie S Willey, Bora Lim, Vicente Valero, Naoto T Ueno, James M Reuben

Faculty, Staff and Student Publications

Circulating tumor cells (CTCs) are indicators of metastatic spread and progression. In a longitudinal, single-center trial of patients with metastatic breast cancer starting a new line of treatment, a microcavity array was used to enrich CTCs from 184 patients at up to 9 timepoints at 3-month intervals. CTCs were analyzed in parallel samples from the same blood draw by imaging and by gene expression profiling to capture CTC phenotypic plasticity. Enumeration of CTCs by image analysis relying primarily on epithelial markers from samples obtained before therapy or at 3-month follow-up identified the patients at the highest risk of progression. CTC …


Molecularly Targeted Therapy In Acute Myeloid Leukemia: Current Treatment Landscape And Mechanisms Of Response And Resistance, Curtis A Lachowiez, Courtney D Dinardo, Sanam Loghavi Mar 2023

Molecularly Targeted Therapy In Acute Myeloid Leukemia: Current Treatment Landscape And Mechanisms Of Response And Resistance, Curtis A Lachowiez, Courtney D Dinardo, Sanam Loghavi

Faculty, Staff and Student Publications

Treatment for acute myeloid leukemia (AML) has evolved rapidly over the last decade as improved understanding of cytogenetic and molecular drivers of leukemogenesis refined survival prognostication and enabled development of targeted therapeutics. Molecularly targeted therapies are now approved for the treatment of FLT3 and IDH1/2-mutated AML and additional molecularly and cellularly targeted therapeutics are in development for defined patient subgroups. Alongside these welcome therapeutic advancements, increased understanding of leukemic biology and treatment resistance has resulted in clinical trials investigating combinations of cytotoxic, cellular, and molecularly targeted therapeutics resulting in improved response and survival outcomes in patients with AML. Herein, …


Qualification Of Hemophilia Treatment Centers To Enable Multi-Center Studies Of Gene Expression Signatures In Blood Cells From Pediatric Patients, Birgit M Reipert, Christoph J Hofbauer, Bagirath Gangadharan, Verena Berg, Elizabeth Donnachie, Shannon Meeks, Maria Elisa Mancuso, Joel Bowen, Deborah L Brown Mar 2023

Qualification Of Hemophilia Treatment Centers To Enable Multi-Center Studies Of Gene Expression Signatures In Blood Cells From Pediatric Patients, Birgit M Reipert, Christoph J Hofbauer, Bagirath Gangadharan, Verena Berg, Elizabeth Donnachie, Shannon Meeks, Maria Elisa Mancuso, Joel Bowen, Deborah L Brown

Faculty, Staff and Student Publications

Hemophilia A is a rare congenital bleeding disorder caused by a deficiency of functionally active coagulation factor VIII (FVIII). Most patients with the severe form of the disease require FVIII replacement therapies, which are often associated with the development of neutralizing antibodies against FVIII. Why some patients develop neutralizing antibodies while others do not is not fully understood. Previously, we could demonstrate that the analysis of FVIII-induced gene expression signatures in peripheral blood mononuclear cells (PBMC) obtained from patients exposed to FVIII replacement therapies provides novel insights into underlying immune mechanisms regulating the development of different populations of FVIII-specific antibodies. …


Treatment Outcomes For Newly Diagnosed, Treatment-Naïve Tp53-Mutated Acute Myeloid Leukemia: A Systematic Review And Meta-Analysis, Naval G Daver, Shahed Iqbal, Camille Renard, Rebecca J Chan, Ken Hasegawa, Hao Hu, Preston Tse, Jiajun Yan, Michael J Zoratti, Feng Xie, Giridharan Ramsingh Mar 2023

Treatment Outcomes For Newly Diagnosed, Treatment-Naïve Tp53-Mutated Acute Myeloid Leukemia: A Systematic Review And Meta-Analysis, Naval G Daver, Shahed Iqbal, Camille Renard, Rebecca J Chan, Ken Hasegawa, Hao Hu, Preston Tse, Jiajun Yan, Michael J Zoratti, Feng Xie, Giridharan Ramsingh

Faculty, Staff and Student Publications

Background: TP53 mutations, which are present in 5% to 10% of patients with acute myeloid leukemia (AML), are associated with treatment resistance and poor outcomes. First-line therapies for TP53-mutated (TP53m) AML consist of intensive chemotherapy (IC), hypomethylating agents (HMA), or venetoclax combined with HMA (VEN + HMA).

Methods: We conducted a systematic review and meta-analysis to describe and compare treatment outcomes in newly diagnosed treatment-naïve patients with TP53m AML. Randomized controlled trials, single-arm trials, prospective observational studies, and retrospective studies were included that reported on complete remission (CR), CR with incomplete hematologic recovery (CRi), overall survival (OS), event-free survival (EFS), …


Mechanosensitive Membrane Proteins: Usual And Unusual Suspects In Mediating Mechanotransduction, Miriam B Goodman, Elizabeth S Haswell, Valeria Vásquez Mar 2023

Mechanosensitive Membrane Proteins: Usual And Unusual Suspects In Mediating Mechanotransduction, Miriam B Goodman, Elizabeth S Haswell, Valeria Vásquez

Faculty, Staff and Student Publications

This Viewpoint, which accompanies a Special Issue focusing on membrane mechanosensors, discusses unifying and unique features of both established and emerging mechanosensitive (MS) membrane proteins, their distribution across protein families and phyla, and current and future challenges in the study of these important proteins and their partners. MS membrane proteins are essential for tissue development, cellular motion, osmotic homeostasis, and sensing external and self-generated mechanical cues like those responsible for touch and proprioception. Though researchers' attention and this Viewpoint focus on a few famous ion channels that are considered the usual suspects as MS mechanosensors, we also discuss some of …


Microbiome Influencers Of Checkpoint Blockade-Associated Toxicity, Yinghong Wang, Robert R Jenq, Jennifer A Wargo, Stephanie S Watowich Mar 2023

Microbiome Influencers Of Checkpoint Blockade-Associated Toxicity, Yinghong Wang, Robert R Jenq, Jennifer A Wargo, Stephanie S Watowich

Faculty, Staff and Student Publications

Immunotherapy has greatly improved cancer outcomes, yet variability in response and off-target tissue damage can occur with these treatments, including immune checkpoint inhibitors (ICIs). Multiple lines of evidence indicate the host microbiome influences ICI response and risk of immune-related adverse events (irAEs). As the microbiome is modifiable, these advances indicate the potential to manipulate microbiome components to increase ICI success. We discuss microbiome features associated with ICI response, with focus on bacterial taxa and potential immune mechanisms involved in irAEs, and the overall goal of driving novel approaches to manipulate the microbiome to improve ICI efficacy while avoiding irAE risk.


The Fly Homolog Of Supt16h, A Gene Associated With Neurodevelopmental Disorders, Is Required In A Cell-Autonomous Fashion For Cell Survival, Mengqi Ma, Xi Zhang, Yiming Zheng, Shenzhao Lu, Xueyang Pan, Xiao Mao, Hongling Pan, Hyung-Lok Chung, Hua Wang, Hong Guo, Hugo J Bellen Mar 2023

The Fly Homolog Of Supt16h, A Gene Associated With Neurodevelopmental Disorders, Is Required In A Cell-Autonomous Fashion For Cell Survival, Mengqi Ma, Xi Zhang, Yiming Zheng, Shenzhao Lu, Xueyang Pan, Xiao Mao, Hongling Pan, Hyung-Lok Chung, Hua Wang, Hong Guo, Hugo J Bellen

Faculty, Staff and Students Publications

SUPT16H encodes the large subunit of the FAcilitate Chromatin Transcription (FACT) complex, which functions as a nucleosome organizer during transcription. We identified two individuals from unrelated families carrying de novo missense variants in SUPT16H. The probands exhibit global developmental delay, intellectual disability, epilepsy, facial dysmorphism and brain structural abnormalities. We used Drosophila to characterize two variants: p.T171I and p.G808R. Loss of the fly ortholog, dre4, causes lethality at an early developmental stage. RNAi-mediated knockdown of dre4 in either glia or neurons causes severely reduced eclosion and longevity. Tissue-specific knockdown of dre4 in the eye or wing leads to the loss …


Whole-Exome Sequencing Study Identifies Four Novel Gene Loci Associated With Diabetic Kidney Disease, Yang Pan, Xiao Sun, Xuenan Mi, Zhijie Huang, Yenchih Hsu, James E Hixson, Donna Munzy, Ginger Metcalf, Nora Franceschini, Adrienne Tin, Anna Köttgen, Michael Francis, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium Topmed Kidney Function Working Group, Jennifer A Brody, Bryan Kestenbaum, Colleen M Sitlani, Josyf C Mychaleckyj, Holly Kramer, Leslie A Lange, Xiuqing Guo, Shih-Jen Hwang, Marguerite R Irvin, Jennifer A Smith, Lisa R Yanek, Dhananjay Vaidya, Yii-Der Ida Chen, Myriam Fornage, Donald M Lloyd-Jones, Lifang Hou, Rasika A Mathias, Braxton D Mitchell, Patricia A Peyser, Sharon L R Kardia, Donna K Arnett, Adolfo Correa, Laura M Raffield, Ramachandran S Vasan, L Adrienne Cupple, Daniel Levy, Robert C Kaplan, Kari E North, Jerome I Rotter, Charles Kooperberg, Alexander P Reiner, Bruce M Psaty, Russell P Tracy, Richard A Gibbs, Alanna C Morrison, Harold Feldman, Eric Boerwinkle, Jiang He, Tanika N Kelly, Cric Study Investigators Mar 2023

Whole-Exome Sequencing Study Identifies Four Novel Gene Loci Associated With Diabetic Kidney Disease, Yang Pan, Xiao Sun, Xuenan Mi, Zhijie Huang, Yenchih Hsu, James E Hixson, Donna Munzy, Ginger Metcalf, Nora Franceschini, Adrienne Tin, Anna Köttgen, Michael Francis, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium Topmed Kidney Function Working Group, Jennifer A Brody, Bryan Kestenbaum, Colleen M Sitlani, Josyf C Mychaleckyj, Holly Kramer, Leslie A Lange, Xiuqing Guo, Shih-Jen Hwang, Marguerite R Irvin, Jennifer A Smith, Lisa R Yanek, Dhananjay Vaidya, Yii-Der Ida Chen, Myriam Fornage, Donald M Lloyd-Jones, Lifang Hou, Rasika A Mathias, Braxton D Mitchell, Patricia A Peyser, Sharon L R Kardia, Donna K Arnett, Adolfo Correa, Laura M Raffield, Ramachandran S Vasan, L Adrienne Cupple, Daniel Levy, Robert C Kaplan, Kari E North, Jerome I Rotter, Charles Kooperberg, Alexander P Reiner, Bruce M Psaty, Russell P Tracy, Richard A Gibbs, Alanna C Morrison, Harold Feldman, Eric Boerwinkle, Jiang He, Tanika N Kelly, Cric Study Investigators

Faculty, Staff and Students Publications

Diabetic kidney disease (DKD) is recognized as an important public health challenge. However, its genomic mechanisms are poorly understood. To identify rare variants for DKD, we conducted a whole-exome sequencing (WES) study leveraging large cohorts well-phenotyped for chronic kidney disease and diabetes. Our two-stage WES study included 4372 European and African ancestry participants from the Chronic Renal Insufficiency Cohort and Atherosclerosis Risk in Communities studies (stage 1) and 11 487 multi-ancestry Trans-Omics for Precision Medicine participants (stage 2). Generalized linear mixed models, which accounted for genetic relatedness and adjusted for age, sex and ancestry, were used to test associations between …


Assigning Pathogenicity For Tab2 Variants Using A Novel Scalable Functional Assay And Expanding Tab2 Disease Spectrum, Weiyi Xu, Andrea Graves, Monika Weisz-Hubshman, Lamees Hegazy, Christina Magyar, Zian Liu, Eleni Nasiotis, Md Abul Hassan Samee, Thomas Burris, Seema Lalani, Lilei Zhang Mar 2023

Assigning Pathogenicity For Tab2 Variants Using A Novel Scalable Functional Assay And Expanding Tab2 Disease Spectrum, Weiyi Xu, Andrea Graves, Monika Weisz-Hubshman, Lamees Hegazy, Christina Magyar, Zian Liu, Eleni Nasiotis, Md Abul Hassan Samee, Thomas Burris, Seema Lalani, Lilei Zhang

Faculty, Staff and Students Publications

Haploinsufficiency of TGF-beta-activated kinase 1 (MAP3K7) binding protein 2 (TAB2) has been associated with congenital heart disease and more recently multiorgan structural abnormalities. Missense variant represents a major proportion of non-synonymous TAB2 variants reported in gnomAD (295/576) and Clinvar (16/73), most of which are variants of uncertain significance (VUSs). However, interpretation of TAB2 missense variants remains challenging because of lack of functional assays. To address this issue, we established a cell-based luciferase assay that enables high-throughput screening of TAB2 variants to assess the functional consequence for predicting variant pathogenicity. Using this platform, we screened 47 TAB2 variants including five pathogenic …


Force–Velocity Profiles In Crossfit Athletes: A Cross-Sectional Study Considering Sex, Age, And Training Frequency, Juan Antonio Párraga-Montilla, José Carlos Cabrera Linares, Pedro Jiménez Reyes, Manuel Moyano López, Victor Serrano Huete, José Alfonso Morcillo Losa, Pedro Ángel Latorre Román Mar 2023

Force–Velocity Profiles In Crossfit Athletes: A Cross-Sectional Study Considering Sex, Age, And Training Frequency, Juan Antonio Párraga-Montilla, José Carlos Cabrera Linares, Pedro Jiménez Reyes, Manuel Moyano López, Victor Serrano Huete, José Alfonso Morcillo Losa, Pedro Ángel Latorre Román

Baltic Journal of Health and Physical Activity

Introduction: The force–velocity profile has been analysed previously in different sports modalities; nevertheless, it has not been analysed in CrossFit. Objective: The aim of this study was to report neuromuscular characteristics of CrossFit athletes using their individual force-velocity profile, investigating differences according to sex, age, and training frequency. Materials and Methods: 72 males (33.17 ± 6.86 years; BMI: 25.93 ± 3.64 kg/m2) and 18 females (30.11 ± 6.92 years; BMI: 23.53 ± 3.98 kg/m2) participated in this study. The force-velocity profile was calculated using Samozino’s method. Furthermore, neuromuscular characterization was completed with a squat jump and …


Characteristics Of The Efficiency Of Actions Of Top-Level Goalkeepers In Soccer, Andrzej Szwarc, Michał Chamera, Henryk Duda, Daniel Memmert, Lukasz Radziminski Mar 2023

Characteristics Of The Efficiency Of Actions Of Top-Level Goalkeepers In Soccer, Andrzej Szwarc, Michał Chamera, Henryk Duda, Daniel Memmert, Lukasz Radziminski

Baltic Journal of Health and Physical Activity

The aim of this study was to present the characteristics of the actions efficiency in elite goalkeepers. 54 observations of 25 goalkeepers participating in 27 matches of the World and the European Championships and the Africa Cup of Nations and Copa America held in the years 2014–2019 were included. The study applied a method of observation. Game data were registered on a self-developed observation sheet. Goalkeepers’ activity, effectiveness, and reliability with a view to implementing the objectives of the game were analyzed in offensive and in defense. It was found that in the elite goalkeepers’ game, offensive actions constitute 62% …


A Trinetx Registry Analysis Of The Need For Second Procedures Following Index Anterior And Posterior Urethroplasty, Zachary J. Prebay, Adam M. Ostrovsky, Matthew Buck, Paul H. Chung Mar 2023

A Trinetx Registry Analysis Of The Need For Second Procedures Following Index Anterior And Posterior Urethroplasty, Zachary J. Prebay, Adam M. Ostrovsky, Matthew Buck, Paul H. Chung

Department of Urology Faculty Papers

Background: We queried a global database to understand re-intervention rates following urethroplasty with the goal of evaluating whether they align with previously published data. Methods: Using the TriNetX database and Common Procedural Terminology (CPT) and International Classification of Diseases-10 (ICD) codes, we identified adult male patients with urethral stricture disease (ICD N35) who underwent one-stage anterior (CPT 53410) or posterior urethroplasty (CPT 53415), with or without (substitution urethroplasty) a tissue flap (CPT 15740) or buccal graft (CPT 15240 or 15241). We set urethroplasty as the index event and used descriptive statistics to report the incidence of secondary procedures (using CPT …


Analysis Of The Adductors And Abductors' Maximum Isometric Strength On The Level Of Speed And Agility In Basketball Players, Paulina Królikowska, Piotr Rodak, Monika Papla, Wojciech Grzyb, Artur Gołaś Mar 2023

Analysis Of The Adductors And Abductors' Maximum Isometric Strength On The Level Of Speed And Agility In Basketball Players, Paulina Królikowska, Piotr Rodak, Monika Papla, Wojciech Grzyb, Artur Gołaś

Baltic Journal of Health and Physical Activity

Introduction: his study investigated the relationship between hip abductor strength (Abd), adductor strength (Add), straight accelerations and decelerations, and during changes of direction (COD 90°) performance in basketball players.

Material and Methods: Fourteen basketball players participated (age = 23.6 ± 4.4 years, body mass = 86.3 ± 5.9 kg, body height = 192.3 ± 6.2 cm, training experience = 6.7 ± 2.6 years). Straight running results and running with a change of direction (COD 90°) have been described as the time (s) obtained for a given length. Following tests were carried out: maximum isometric strength test, 20-m linear sprint and …


Population Pharmacokinetics And Exposure–Response Analysis For The Phase 3 Cosmic-311 Trial Of Cabozantinib For Radioiodine-Refractory Differentiated Thyroid Cancer, Neang S. Ly, Jing Li, Raffaella Faggioni, Lorin K. Roskos, Marcia S Brose Mar 2023

Population Pharmacokinetics And Exposure–Response Analysis For The Phase 3 Cosmic-311 Trial Of Cabozantinib For Radioiodine-Refractory Differentiated Thyroid Cancer, Neang S. Ly, Jing Li, Raffaella Faggioni, Lorin K. Roskos, Marcia S Brose

Kimmel Cancer Center Faculty Papers

Background and Objective

In the USA, cabozantinib was approved for the treatment of patients aged ≥ 12 years with radioiodine-refractory differentiated thyroid cancer (DTC) who progressed on prior vascular endothelial growth factor (VEGFR)-targeted therapy based on the Phase 3 COSMIC-311 trial, which evaluated cabozantinib 60 mg/day versus placebo. Approved dosing is 60 mg/day for adults and for pediatric patients aged ≥ 12 years with body surface area (BSA) ≥ 1.2 m2, and 40 mg/day for pediatric patients aged ≥ 12 years with BSA < 1.2 m2. This report describes a population pharmacokinetic (PopPK) and exposure–response analysis of COSMIC-311.

Methods

A PopPK model was developed using concentration-time data from COSMIC-311 and 6 other cabozantinib studies. The …


Ablation Of Rare Accessory Pathway From Right Atrial Appendage Diverticulum To Anatomic Left Ventricle In Cc-Tga., Shree Lata Radhakrishnan, Robert Drutel, Cody Williams, Raman Danrad, Kelly Gajewski, Paul A. Lelorier Mar 2023

Ablation Of Rare Accessory Pathway From Right Atrial Appendage Diverticulum To Anatomic Left Ventricle In Cc-Tga., Shree Lata Radhakrishnan, Robert Drutel, Cody Williams, Raman Danrad, Kelly Gajewski, Paul A. Lelorier

School of Medicine Faculty Publications

American College of Cardiology Conference ACC.23, March 4 - 6, 2023, New Orleans, LA