Medical Specialties Commons^™

The Impact Of Genetic Ancestry On Survival Outcomes In Pediatric Rhabdomyosarcoma: A Report From The Children’S Oncology Group, Ekene A Onwuka, Christina L Magyar, Bailey A Martin-Giacalone, Michael E Scheurer, Deborah A Marquez-Do, Mark Zobeck, Elizabeth G Atkinson, Erin R Rudzinski, Michael A Arnold, Donald A Barkauskas, David Hall, Javed Khan, Jack F Shern, Paul Scheet, Brian Crompton, Corinne M Linardic, Douglas S Hawkins, Rajkumar Venkatramani, Lisa Mirabello, Chad D Huff, Melissa A Richard, Philip J Lupo

Faculty, Staff and Student Publications

Emerging evidence suggests genetic ancestry may influence childhood cancer outcomes, but its impact on pediatric rhabdomyosarcoma (RMS) is unknown. We explored genetic ancestry's impact on survival among children with RMS. This multi-center observational cohort study is a secondary analysis of previously collected biobanking, genomic, and clinical data. The study included 920 individuals with newly diagnosed RMS under 40 years of age enrolled from 2005 to 2017 under the COG soft tissue sarcoma biobanking protocol D9902. The primary endpoints were (1) event-free survival (EFS), defined as the time from study enrollment to tumor recurrence/progression, secondary malignancy, or death from any cause; …

Prognostic Value Of Lipoprotein(A) For Cardiovascular Events After Lower Limb Revascularization In Diabetic Patients With Chronic Limb-Threatening Ischemia, Federico Biscetti, Maria Margherita Rando, Maria Anna Nicolazzi, Flavia Angelini, Roberto Iezzi, Luis H. Eraso, Paul J. Dimuzio, Dario Pitocco, Massimo Massetti, Antonio Gasbarrini, Andrea Flex

Department of Surgery Faculty Papers

BACKGROUND: Chronic limb-threatening ischemia (CLTI) presents a major clinical challenge in patients with Type 2 Diabetes Mellitus (T2DM), requiring lower extremity revascularization (LER) to mitigate adverse cardiovascular and limb outcomes. Lipoprotein(a) (Lp(a)) has been implicated in cardiovascular risk, but its role in patients with T2DM and CLTI undergoing revascularization remains unclear. Thus, this study aimed to investigate the prognostic value of Lp(a) levels in diabetic CLTI patients for major adverse cardiovascular events (MACE), major adverse limb events (MALE), or both after LER.

METHODS: In this prospective cohort study of 158 individuals with T2DM and CLTI undergoing LER, baseline clinical data …

Measles Assessment And Treatment, Bob Underwood, Edward Lyon

Pediatrics in Practice: A CME Podcast

Eddie Lyon, MD, discusses concerns related to an uptick in measles cases, and how community providers can assess, limit exposure and guide patients to remain healthy.

Click here to stream the podcast episode.

First-In-Human Phase I Open-Label Study Of The Anti-Tim-3 Monoclonal Antibody Incagn02390 In Patients With Select Advanced Or Metastatic Solid Tumors, Martin E. Gutierrez, Shou Ching Tang, John D. Powderly, Ani S. Balmanoukian, Paul E. Hoyle, Zhiwan Dong, Lulu Cheng, Xiaohua Gong, John E. Janik, Nawel Bourayou, Omid Hamid

School of Medicine Faculty Publications

Background T-cell immunoglobulin and mucin domain-containing protein-3 (TIM-3) is an immune checkpoint receptor upregulated during anti-programmed death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) immunotherapy for cancer. TIM-3 blockade may improve the antitumor activity of PD-1/PD-L1inhibition. This phase 1 study evaluated INCAGN02390, a novel, fully human Fc-engineered antibody against TIM-3. Methods INCAGN02390 was evaluated by dose escalation at 10-1600 mg infused in 14-day cycles (every 2 weeks [Q2W]) in pretreated patients with select advanced/metastatic immunogenic solid tumors. Objectives included evaluation of safety/tolerability and maximum tolerated dose (MTD) (primary), pharmacokinetics, preliminary antitumor activity, pharmacodynamics, and immunogenicity (secondary). Results Forty patients were enrolled and …

Genome Report: Whole-Genome Assembly Of The Relapsing Fever Tick Ornithodoros Turicata Dugès (Acari: Argasidae), Mackenzie Tietjen, Amanda R Stahlke, David Luecke, Perot Saelao, Sheina B Sim, Scott M Geib, Brian E Scheffler, Anna K Childers, Alexander R Kneubehl, Pete D Teel, Job E Lopez

Faculty, Staff and Students Publications

The soft tick family Argasidae contains vectors of medical and veterinary importance, but few molecular resources are available compared to hard ticks (Ixodidae). One example is Ornithodoros turicata, a recognized vector of Borrelia turicatae, causal agent of human relapsing fever, and a putative vector of African swine fever virus. To address the current lack of molecular resources for the Argasidae, we generated a chromosome-level genome assembly for O. turicata using PacBio sequencing in conjunction with an Illumina Hi-C library. The resulting reference genome has a total of 1.1 Gb in length and was assembled into 10 chromosomes and 368 unplaced …

Clinically Important Endpoints In Individuals With Leukodystrophy: A Multisite Study, Emma R Kotes, Sarah Woidill, Russell D'Aiello, Amina Khan, Jacob Mccann, Mark Ramos, Francesco Gavazzi, Stephanie Keller, Keith Van Haren, Ali Fatemi, Florian Eichler, Joshua Bonkowsky, Jamie Fraser, Lisa Emrick, Omar Sherbini, Ashley Hackett, Jeilo Gauna, Dandre Amos, Jordan Goodman, Amena Smith Fine, Amanda Nagy, Seungil Lee, Nicole Page, Johanna Schmidt, Amy Pizzino, Kayla Muirhead, Mariko Bennett, Amy Waldman, Justine Shults, Laura Adang, Robert Grundmeier, Adeline Vanderver

Faculty, Staff and Students Publications

Importance: Leukodystrophies are a diverse group of rare disorders that disrupt central myelination. These disorders present with a broad spectrum of neurologic severity and are associated with a range of potential secondary complications, such as scoliosis and failure of independent feeding.

Objective: we explore real-world data of leukodystrophy complications to inform future evidence-based care guidelines across these rare diseases.

Design: In a cross-sectional observational study, we use a leukodystrophy-specific research consortium and the availability of electronic health records (EHR) to capture a cross-section of real-world data.

Setting: Subjects were identified using EHR data from five hospital systems with established expertise …

Inferring Chromosome Segregation Error Stage And Crossover In Trisomic Disorders With Application To Down Syndrome, Zhenhua Li, Wenjian Yang, Gang Wu, Ti-Cheng Chang, Zhongshan Cheng, Meenakshi Devidas, Mary Shago, Andrew J Carroll, Nyla A Heerema, Julie M Gastier-Foster, Brent L Wood, Lauren Sanclemente, Elizabeth A Raetz, Stephen P Hunger, Mignon L Loh, Eleanor Feingold, Tracie C Rosser, Emily G Allen, Stephanie L Sherman, Karen R Rabin, Philip J Lupo, Jun J Yang

Faculty, Staff and Students Publications

Errors in chromosome segregation during gametogenesis, such as nondisjunction (NDJ) errors, have severe consequences in human reproduction, and a better understanding of their etiology is of fundamental interest in genetics. Mapping NDJ errors to meiotic/mitotic stages typically requires proband-parent comparison, limiting its applicability. Herein, we develop Mis-segregation Error Identification through Hidden Markov Models (MeiHMM), a method for inferring NDJ error stage and crossover events based on only genomic data of trisomic probands. Guided by triallelic genotype/haplotype configurations, MeiHMM discerns the allelic origin at each locus, which informs NDJ error during gamete formation, without identifying the parental origin of the trisomy. …

Single-Cell Profiling Of Bone Metastasis Ecosystems From Multiple Cancer Types Reveals Convergent And Divergent Mechanisms Of Bone Colonization, Fengshuo Liu, Yunfeng Ding, Zhan Xu, Xiaoxin Hao, Tianhong Pan, George Miles, Siyue Wang, Yi-Hsuan Wu, Jun Liu, Igor L Bado, Weijie Zhang, Ling Wu, Yang Gao, Liqun Yu, David G Edwards, Hilda L Chan, Sergio Aguirre, Michael Warren Dieffenbach, Elina Chen, Yichao Shen, Dane Hoffman, Luis Becerra Dominguez, Charlotte Helena Rivas, Xiang Chen, Hai Wang, Zbigniew Gugala, Robert L Satcher, Xiang H-F Zhang

Faculty, Staff and Students Publications

Bone is a common site for metastasis of solid cancers. The diversity of histological and molecular characteristics of bone metastases (BMs) remains poorly studied. Here, we performed single-cell RNA sequencing on 42 BMs from eight cancer types, identifying three distinct ecosystem archetypes, each characterized by an enrichment of specific immune cells: macrophages/osteoclasts, regulatory/exhausted T cells, or monocytes. We validated these archetypes by immunostaining on tissue sections and bioinformatic analysis of bulk RNA sequencing/microarray data from 158 BMs across more than 10 cancer types. Interestingly, we found only a modest correlation between the BM archetypes and the tissues of origin; BMs …

Systematic Analysis Of Nonsense Variants Uncovers Peptide Release Rate As A Novel Modifier Of Nonsense-Mediated Mrna Decay, Divya Kolakada, Rui Fu, Nikita Biziaev, Alexey Shuvalov, Mlana Lore, Amy E Campbell, Michael A Cortázar, Marcin P Sajek, Jay R Hesselberth, Neelanjan Mukherjee, Elena Alkalaeva, Zeynep H Coban-Akdemir, Sujatha Jagannathan

Faculty, Staff and Student Publications

The phenotypic impact of nonsense variants is determined by nonsense-mediated mRNA decay (NMD), which degrades transcripts with premature termination codons (PTCs). Despite the clinical importance of nonsense variants, transcript-specific and context-dependent variations in NMD activity remain poorly understood. Here, we show that the amino acid preceding the PTC strongly influences NMD activity. Glycine codons promote robust NMD efficiency and show striking enrichment before PTCs but are depleted before normal termination codons. Glycine-PTC enrichment is particularly pronounced in genes tolerant to loss-of-function variants, suggesting efficient elimination of truncated proteins from nonessential genes. We further demonstrate that the peptide release rate during …

Wdr2 Regulates The Orphan Kinesin Kin-G To Promote Hook Complex And Golgi Biogenesis In Trypanosoma Brucei, Qing Zhou, Huiqing Hu, Ziyin Li

Faculty, Staff and Student Publications

The flagellum in Trypanosoma brucei plays crucial roles in cell locomotion, cell morphogenesis, and cell division, and its inheritance depends on the faithful duplication of multiple flagellum-associated structures. One of such cytoskeletal structures is a hairpin-like structure termed the hook complex, composed of a fishhook-like structure and a centrin arm structure, whose cellular functions remain poorly understood. We recently identified KIN-G, an orphan kinesin that promotes hook complex and Golgi biogenesis. Here we report a WD40 repeat-containing protein named WD40 Repeat-containing protein 2 (WDR2), which interacts with and regulates KIN-G. WDR2 co-localizes with KIN-G at the centrin arm, and knockdown …

From Novice To Expert: Preparing Your Peer Review, Diana M Proctor, Rachy Abraham, Shannon Esher Righi

Faculty, Staff and Student Publications

Peer review is the process by which the quality of scholarly work is assessed prior to being published, presented, or funded. The consequences of flawed research entering the public domain in the "post-truth" era highlight the need to improve peer review quality, which we believe can be achieved by standardizing training. Here, we aim to enhance the quality of published literature by presenting a systematic guide to train new reviewers (and aid experienced ones) in the art of peer reviewing the rigor of scientific manuscripts.

Flipping The Curriculum For Resident Didactics: In-Training And Certifying Examination Scores In An Internal Medicine Residency, Luke Mccoy, Ronald J. Markert, Elysha Thoms, Olivia Noall, Kathryn Burtson

Internal Medicine Faculty Publications

Purpose The flipped classroom (FC) model is increasingly used in undergraduate medical education, where it has been associated with improved knowledge acquisition. However, its impact on graduate medical education (GME) remains underexplored. We hypothesized that implementing a flipped didactics curriculum in our internal medicine residency program would improve performance on the Internal Medicine In-Training Examination (IM-ITE) and the American Board of Internal Medicine Certifying Examination (IM-CE). Methods In 2017, we transitioned from a traditional lecture-based (LB) curriculum to a flipped model. Noon conferences were replaced with problem-based learning (PBL) sessions three days per week, with additional active learning formats used …

Pulsed Field Ablation Of Persistent Atrial Fibrillation With Continuous Electrocardiographic Monitoring Follow-Up: Advantage Af Phase 2., Vivek Y Reddy, Edward P Gerstenfeld, Boris Schmidt, Jason G Andrade, Devi Nair, Andrea Natale, Walid Saliba, Philipp Sommer, Andreas Metzner, Atul Verma, Troy Hounshell, Anish Amin, Philip Gentlesk, Stanislav Weiner, Frank A Cuoco, Jamie Kim, Mohit K Turagam, Gery Tomassoni, Chinmay Patel, Ziad Issa, Michael Shehata, Allison M Anderson, Thomas J Stoltz, Jonathan D Raybuck, Torri Schwartz, Brad S Sutton, Moussa Mansour

Heart and Vascular Articles

BACKGROUND: There are sparse high-quality safety and effectiveness data for pulsed field ablation (PFA) of persistent atrial fibrillation (PerAF), in which lesions beyond pulmonary vein isolation (PVI) are often placed. In addition, no large trials have used insertable cardiac monitors for continuous rhythm monitoring after ablation in patients with PerAF or after PFA in any atrial fibrillation population. In Phase 2 of the ADVANTAGE AF study (A Prospective Single Arm Open Label Study of the FARAPULSE Pulsed Field Ablation System in Subjects With Persistent Atrial Fibrillation), patients with PerAF underwent PFA for PVI and posterior wall ablation (PWA) and, in …

First Quantitative Investigation On The Dosimetric Perturbation From Dental Hardware In Spot-Scanning Proton Arc (Sparc®) Therapy And Planning Strategies In Head Neck Cancer Patient Population, Evan Harbert

Masters Projects

Purpose

There has been a tremendous interest in applying Spot-scanning Proton Arc (SPArc^®) to benefit head and neck cancer (HNC) patient population. However, the dental hardware materials effects on the beam distribution are not well understood, and placing spots through the dental hardware may cause an unnecessary degradation of target coverage if the material components differ from the nominal plan. The purpose of this study is to provide a quantitative dose perturbation analysis of the uncertainties caused by dental hardware and introduce a SPArc^® planning strategy to mitigate such impacts.

Methods and Materials

A published in-house developed …

Systemic Carbonic Anhydrase Inhibitors In Common Ophthalmic Diseases: A Scoping Review From A Clinical Standpoint, Shahin Hallaj, Wesam S. Shalaby, Sapna Sinha, Jonathan S. Myers, Reza Razeghinejad

Wills Eye Hospital Papers

PURPOSE OF REVIEW: This paper provides a detailed overview of systemic carbonic anhydrase inhibitors (CAIs) and their application in managing ophthalmic conditions, including glaucoma, cystoid macular edema, and idiopathic intracranial hypertension. Despite their recognized clinical benefits, the potential for severe systemic adverse effects often discourages clinicians from prescribing these agents. By examining the pharmacology, pharmacokinetics, safety profile, and clinical indications of systemic CAIs, this review highlights strategies to mitigate treatment challenges, particularly in patients with comorbidities and complex medical backgrounds.

RECENT FINDINGS: New insights into the diverse roles and distribution of carbonic anhydrase (CA) isozymes have expanded our understanding of …

Infantile Pyknocytosis Revisited: Possible Familial Trend In A Study Of 9 Patients, Aileen Y Hu, Amy M Coffey, Jyotinder N Punia, Andrea N Marcogliese, Choladda V Curry, M Tarek Elghetany

Faculty, Staff and Students Publications

Context.—: Infantile pyknocytosis (IP) is an uncommon cause of transient neonatal hemolytic anemia and hyperbilirubinemia occurring in approximately 10% of cases of unexplained neonatal hemolytic anemia.

Objective.—: To study cases of IP with focus on long-term follow-up, perinatal events, and family history.

Design.—: Cases were prospectively identified during review of peripheral blood smears for neonatal hyperbilirubinemia during an 11-year period. Clinical and laboratory parameters, follow-up data, and family history were recorded.

Results.—: Nine cases of IP were identified from the morphologic recognition of pyknocytes and clinical and laboratory evidence of hemolysis, and included 6 males and 3 females. Age at …

The Co-Occurrence Of Autism Spectrum Disorder And Aarskog-Scott Syndrome In An Accomplished Young Man, Raisa S Romanova, Oksana I Talantseva, Katerina V Lind, Victoria A Manasevich, Julia E Kuznetsova, Elena L Grigorenko

Faculty, Staff and Students Publications

Objectives/Background: Aarskog-Scott syndrome (AAS), also known as faciogenital dysplasia, is a rare X-linked genetic disorder primarily characterized by its diverse physical manifestations. Previous evidence suggests a potential association between AAS and neurodevelopmental disorders, including autism spectrum disorder (ASD).

Methods: This case study presents a male adolescent with ASD and a novel genetic variant in FGD1 underlying AAS. We conducted comprehensive clinical, genetic, and behavioral assessments to characterize the neurodevelopmental presentation. Moreover, we examined the existing literature on AAS and comorbid neurodevelopmental disorders.

Results: The patient demonstrated features consistent with both AAS and ASD, presenting with characteristic physical features of AAS …

Psilocybin Treatment Extends Cellular Lifespan And Improves Survival Of Aged Mice, Kosuke Kato, Jennifer M Kleinhenz, Yoon-Joo Shin, Cristian Coarfa, Ali J Zarrabi, Louise Hecker

Faculty, Staff and Students Publications

Psilocybin, the naturally occurring psychedelic compound produced by hallucinogenic mushrooms, has received attention due to considerable clinical evidence for its therapeutic potential to treat various psychiatric and neurodegenerative indications. However, the underlying molecular mechanisms remain enigmatic, and few studies have explored its systemic impacts. We provide the first experimental evidence that psilocin (the active metabolite of psilocybin) treatment extends cellular lifespan and psilocybin treatment promotes increased longevity in aged mice, suggesting that psilocybin may be a potent geroprotective agent.

The Benefits Of Exercise Training In Combination With Weight Loss Therapies, Bryan C Jiang, Dennis T Villareal

Faculty, Staff and Students Publications

The primary treatment for obesity involves calorie restriction (CR) to promote dietary weight loss achieved through interventions including behavioral modification, bariatric surgery, and antiobesity medications. In adults with obesity, CR-induced weight loss enhances physical function and improves quality of life, while also reducing the burden of various obesity-related chronic conditions, including hypertension, diabetes, obstructive sleep apnea, and atherosclerotic heart disease. However, it is also associated with a decline in lean mass and bone mineral density, which increases the risk of sarcopenia and osteoporosis. When performed alongside CR, progressive resistance training (RT) attenuates this loss of lean mass and bone mass, …

Younger Haplo-Donors Improve Older Patient Survival Outcomes, Ahmad Ghorab, Leo Luznik

Faculty, Staff and Students Publications

No abstract provided.

Food Noise: Definition, Measurement, And Future Research Directions, Emily J Dhurandhar, Kevin C Maki, Nikhil V Dhurandhar, Theodore K Kyle, Sydney Yurkow, Misty A W Hawkins, Jon Agley, Emily H Ho, Lawrence J Cheskin, Thorkild I A Sørensen, Xi Rita Wang, David B Allison

Children’s Nutrition Research Center Staff Publications

The term food noise has been recently popularized by individuals managing their weight or adhering to specific diets for health reasons. Anecdotal evidence from patients and clinical observations suggests that food noise involves constant preoccupation with food-related decisions-such as which foods to eat, caloric intake, macronutrient balance, and meal timing-which can become intrusive and unpleasant. Food noise also appears to affect cognitive burden and quality of life, and is being cited as one reason weight-loss attempts fail. The increase in public discourse about food noise has highlighted its potential significance, yet a formal clinical definition and method of measurement of …

Extracellular Vesicles In Cancer: From Isolation And Characterization To Metastasis, Drug Resistance, And Clinical Applications, Ancuta Jurj, Doru Paul, George A Calin

Faculty, Staff and Student Publications

Cancer progression, along with other hallmarks of cancer, is sustained through bidirectional cell-to-cell communication. This function is primarily facilitated by lipid-rich nanoparticles expelled into the extracellular matrix by stromal and/or malignant cells. These entities, known as extracellular vesicles, contain a vast repertoire of bioactive molecules and hold promise as potential biomarkers and nanovehicles for drug delivery. Intriguingly, the cellular and molecular mechanisms governing the functions of extracellular vesicles remain poorly understood. In the present manuscript, we highlight the intracellular and intercellular journey of extracellular vesicles, from their inception to the present day, their implications in various hallmarks of cancer, and …

Pi(4)P Recruits Cide Proteins To Promote The Formation Of Unilocular Lipid Droplets During Adipogenesis And Hepatic Steatosis, Jin Wu, Mingming Gao, Xiaoqin Wu, Yang Liu, Taiping Zhang, Yan Liang, Haixia Yang, Chengxin Ma, Youpi Ye, Chunmei Chang, Peng Li, Feng-Jung Chen, Hongyuan Yang

Faculty, Staff and Student Publications

Lipid droplets (LDs) are evolutionarily conserved organelles that play important roles in metabolism. Each LD is enclosed by a monolayer of phospholipids, distinct from bilayer membranes. The composition of LD surface phospholipids and their impact on LD growth and function remain to be defined. Phosphoinositides mark cellular organelles and regulate organellar function. Here, we demonstrate that PI(4)P decorates a subset of LDs to recruit and activate CIDE proteins. Enhanced expression of ORP2 and ORP5, LD-associated lipid transfer proteins that remove PI(4)P from LDs, abolished the localization and function of CIDE proteins. Blocking the synthesis of PI(4)P on the LD surface …

High-Affinity Cd16a Polymorphism Associated With Reduced Risk Ofsevere Covid-19, Anita E Qualls, Tasha Tsao, Irene Lui, Shion A Lim, Yapeng Su, Ernie Chen, Dylan Duchen, Holden T Maecker, Seunghee Kim-Schulze, Ruth R Montgomery, Florian Krammer, Charles R Langelier, Ofer Levy, Lindsey R Baden, Esther Melamed, Lauren Ir Ehrlich, Grace A Mccomsey, Rafick P Sekaly, Charles B Cairns, Elias K Haddad, Albert C Shaw, David A Hafler, David B Corry, Farrah Kheradmand, Mark A Atkinson, Scott C Brakenridge, Nelson I Agudelo Higuita, Jordan P Metcalf, Catherine L Hough, William B Messer, Bali Pulendran, Kari C Nadeau, Mark M Davis, Ana Fernandez-Sesma, Viviana Simon, Monica Kraft, Christian Bime, Carolyn S Calfee, David J Erle, Joanna Schaenmann, Al Ozonoff, Bjoern Peters, Steven H Kleinstein, Alison D Augustine, Joann Diray-Arce, Patrice M Becker, Nadine Rouphael, Impacc Network, Jason D Goldman, Daniel R Calabrese, James R Heath, James A Wells, Elaine F Reed, Lewis L Lanier, Harry Pickering, Oscar A Aguilar

Faculty, Staff and Students Publications

CD16A is an activating Fc receptor on NK cells that mediates antibody-dependent cellular cytotoxicity (ADCC), a key mechanism in antiviral immunity. However, the role of NK cell-mediated ADCC in SARS-CoV-2 infection remains unclear, particularly whether it limits viral spread and disease severity or contributes to the immunopathogenesis of COVID-19. We hypothesized that the high-affinity CD16AV176 polymorphism influences these outcomes. Using an in vitro reporter system, we demonstrated that CD16AV176 is a more potent and sensitive activator than the common CD16AF176 allele. To assess its clinical relevance, we analyzed 1,027 patients hospitalized with COVID-19 from the Immunophenotyping Assessment in a COVID-19 …

Opposing Roles For Myeloid And Smooth Muscle Cell Sting In Pulmonary Hypertension, Ann T Pham, Shiza Virk, Aline C Oliveira, Matthew D Alves, Chunhua Fu, Yutao Zhang, Jimena Alvarez-Castanon, Brian B Lee, Keira L Lee, Radwan Mashina, Katherine E Ray, Patrick Donabedian, Elnaz Ebrahimi, Harsh Patel, Reeha Patel, Duncan Lewis, Zhiguang Huo, Harry Karmouty-Quintana, Li Chen, Lei Jin, Andrew J Bryant

Faculty, Staff and Student Publications

There is an emerging role for stimulator of interferon genes (STING) signaling in pulmonary hypertension (PH) development. Related to this, prior research has demonstrated the relevance of immune checkpoint protein programmed death ligand 1 (PD-L1) expression by immunoregulatory myeloid cells in PH. However, there remains a need to elucidate the cell-specific role of STING expression, and the STING/PD-L1 signaling axis in PH, before readily available disease-modifying therapies can be applied for patients with the disease. Here, through generation of bone marrow chimeric mice, we show that STING-/- mice receiving WT bone marrow were protected against PH secondary to chronic hypoxia. …

Nivolumab Plus Relatlimab For Patients With Relapsed Or Progressed B-Cell Malignancies In Relativity-022, Ajay K Gopal, Philippe Armand, Sattva S Neelapu, Nancy L Bartlett, Stephen E Spurgeon, John Kuruvilla, Kerry J Savage, John P Leonard, Arnold B Gelb, Nasir Ahmed, Shiqi Dong, Sai Praneeth Bathena, Rasika Suryawanshi, Jenny Qun Wu, Sheen Wang, Douglas E Gladstone

Faculty, Staff and Student Publications

Despite high response rates, anti-programmed death 1 (anti-PD-1) monotherapy eventually fails in most patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL) and is ineffective in most other B-cell malignancies. The lymphocyte activation gene 3 (LAG-3) cell-surface receptor represents another immune checkpoint that can be targeted to induce remissions in these diseases; dual inhibition of PD-1 and LAG-3 is approved in advanced melanoma. We performed a multicenter phase 1/2a open-label study of the anti-LAG-3 antibody relatlimab (RELATIVITY-022) administered as monotherapy or in combination with nivolumab in patients with R/R B-cell malignancies. We treated 106 patients and no dose-limiting toxicities were observed during …

Towards Fair Decentralized Benchmarking Of Healthcare Ai Algorithms With The Federated Tumor Segmentation (Fets) Challenge, Maximilian Zenk, Ujjwal Baid, Sarthak Pati, Akis Linardos, Brandon Edwards, Micah Sheller, Patrick Foley, Alejandro Aristizabal, David Zimmerer, Alexey Gruzdev, Jason Martin, Russell T Shinohara, Annika Reinke, Fabian Isensee, Santhosh Parampottupadam, Kaushal Parekh, Ralf Floca, Hasan Kassem, Bhakti Baheti, Siddhesh Thakur, Verena Chung, Kaisar Kushibar, Karim Lekadir, Meirui Jiang, Youtan Yin, Hongzheng Yang, Quande Liu, Cheng Chen, Qi Dou, Pheng-Ann Heng, Xiaofan Zhang, Shaoting Zhang, Muhammad Irfan Khan, Mohammad Ayyaz Azeem, Mojtaba Jafaritadi, Esa Alhoniemi, Elina Kontio, Suleiman A Khan, Leon Mächler, Ivan Ezhov, Florian Kofler, Suprosanna Shit, Johannes C Paetzold, Timo Loehr, Benedikt Wiestler, Himashi Peiris, Kamlesh Pawar, Shenjun Zhong, Zhaolin Chen, Munawar Hayat, Gary Egan, Mehrtash Harandi, Ece Isik Polat, Gorkem Polat, Altan Kocyigit, Alptekin Temizel, Anup Tuladhar, Lakshay Tyagi, Raissa Souza, Nils D Forkert, Pauline Mouches, Matthias Wilms, Vishruth Shambhat, Akansh Maurya, Shubham Subhas Danannavar, Rohit Kalla, Vikas Kumar Anand, Ganapathy Krishnamurthi, Sahil Nalawade, Chandan Ganesh, Ben Wagner, Divya Reddy, Yudhajit Das, Fang F Yu, Baowei Fei, Ananth J Madhuranthakam, Joseph Maldjian, Gaurav Singh, Jianxun Ren, Wei Zhang, Ning An, Qingyu Hu, Youjia Zhang, Ying Zhou, Vasilis Siomos, Giacomo Tarroni, Jonathan Passerrat-Palmbach, Ambrish Rawat, Giulio Zizzo, Swanand Ravindra Kadhe, Jonathan P Epperlein, Stefano Braghin, Yuan Wang, Renuga Kanagavelu, Qingsong Wei, Yechao Yang, Yong Liu, Krzysztof Kotowski, Szymon Adamski, Bartosz Machura, Wojciech Malara, Lukasz Zarudzki, Jakub Nalepa, Yaying Shi, Hongjian Gao, Salman Avestimehr, Yonghong Yan, Agus S Akbar, Ekaterina Kondrateva, Hua Yang, Zhaopei Li, Hung-Yu Wu, Johannes Roth, Camillo Saueressig, Alexandre Milesi, Quoc D Nguyen, Nathan J Gruenhagen, Tsung-Ming Huang, Jun Ma, Har Shwinder H Singh, Nai-Yu Pan, Dingwen Zhang, Ramy A Zeineldin, Michal Futrega, Yading Yuan, Gian Marco Conte, Xue Feng, Quan D Pham, Yong Xia, Zhifan Jiang, Huan Minh Luu, Mariia Dobko, Alexandre Carré, Bair Tuchinov, Hassan Mohy-Ud-Din, Saruar Alam, Anup Singh, Nameeta Shah, Weichung Wang, Chiharu Sako, Michel Bilello, Satyam Ghodasara, Suyash Mohan, Christos Davatzikos, Evan Calabrese, Jeffrey Rudie, Javier Villanueva-Meyer, Soonmee Cha, Christopher Hess, John Mongan, Madhura Ingalhalikar, Manali Jadhav, Umang Pandey, Jitender Saini, Raymond Y Huang, Ken Chang, Minh-Son To, Sargam Bhardwaj, Chee Chong, Marc Agzarian, Michal Kozubek, Filip Lux, Jan Michálek, Petr Matula, Miloš Ker Kovský, Tereza Kopr Ivová, Marek Dostál, Václav Vybíhal, Marco C Pinho, James Holcomb, Marie Metz, Rajan Jain, Matthew D Lee, Yvonne W Lui, Pallavi Tiwari, Ruchika Verma, Rohan Bareja, Ipsa Yadav, Jonathan Chen, Neeraj Kumar, Yuriy Gusev, Krithika Bhuvaneshwar, Anousheh Sayah, Camelia Bencheqroun, Anas Belouali, Subha Madhavan, Rivka R Colen, Aikaterini Kotrotsou, Philipp Vollmuth, Gianluca Brugnara, Chandrakanth J Preetha, Felix Sahm, Martin Bendszus, Wolfgang Wick, Abhishek Mahajan, Carmen Balaña, Jaume Capellades, Josep Puig, Yoon Seong Choi, Seung-Koo Lee, Jong Hee Chang, Sung Soo Ahn, Hassan F Shaykh, Alejandro Herrera-Trujillo, Maria Trujillo, William Escobar, Ana Abello, Jose Bernal, Jhon Gómez, Pamela Lamontagne, Daniel S Marcus, Mikhail Milchenko, Arash Nazeri, Bennett Landman, Karthik Ramadass, Kaiwen Xu, Silky Chotai, Lola B Chambless, Akshitkumar Mistry, Reid C Thompson, Ashok Srinivasan, J Rajiv Bapuraj, Arvind Rao, Nicholas Wang, Ota Yoshiaki, Toshio Moritani, Sevcan Turk, Joonsang Lee, Snehal Prabhudesai, John Garrett, Matthew Larson, Robert Jeraj, Hongwei Li, Tobias Weiss, Michael Weller, Andrea Bink, Bertrand Pouymayou, Sonam Sharma, Tzu-Chi Tseng, Saba Adabi, Alexandre Xavier Falcão, Samuel B Martins, Bernardo C A Teixeira, Flávia Sprenger, David Menotti, Diego R Lucio, Simone P Niclou, Olivier Keunen, Ann-Christin Hau, Enrique Pelaez, Heydy Franco-Maldonado, Francis Loayza, Sebastian Quevedo, Richard Mckinley, Johannes Slotboom, Piotr Radojewski, Raphael Meier, Roland Wiest, Johannes Trenkler, Josef Pichler, Georg Necker, Andreas Haunschmidt, Stephan Meckel, Pamela Guevara, Esteban Torche, Cristobal Mendoza, Franco Vera, Elvis Ríos, Eduardo López, Sergio A Velastin, Joseph Choi, Stephen Baek, Yusung Kim, Heba Ismael, Bryan Allen, John M Buatti, Peter Zampakis, Vasileios Panagiotopoulos, Panagiotis Tsiganos, Sotiris Alexiou, Ilias Haliassos, Evangelia I Zacharaki, Konstantinos Moustakas, Christina Kalogeropoulou, Dimitrios M Kardamakis, Bing Luo, Laila M Poisson, Ning Wen, Martin Vallières, Mahdi Ait Lhaj Loutfi, David Fortin, Martin Lepage, Fanny Morón, Jacob Mandel, Gaurav Shukla, Spencer Liem, Gregory S Alexandre, Joseph Lombardo, Joshua D Palmer, Adam E Flanders, Adam P Dicker, Godwin Ogbole, Dotun Oyekunle, Olubunmi Odafe-Oyibotha, Babatunde Osobu, Mustapha Shu'aibu Hikima, Mayowa Soneye, Farouk Dako, Adeleye Dorcas, Derrick Murcia, Eric Fu, Rourke Haas, John A Thompson, David Ryan Ormond, Stuart Currie, Kavi Fatania, Russell Frood, Amber L Simpson, Jacob J Peoples, Ricky Hu, Danielle Cutler, Fabio Y Moraes, Anh Tran, Mohammad Hamghalam, Michael A Boss, James Gimpel, Deepak Kattil Veettil, Kendall Schmidt, Lisa Cimino, Cynthia Price, Brian Bialecki, Sailaja Marella, Charles Apgar, Andras Jakab, Marc-André Weber, Errol Colak, Jens Kleesiek, John B Freymann, Justin S Kirby, Lena Maier-Hein, Jake Albrecht, Peter Mattson, Alexandros Karargyris, Prashant Shah, Bjoern Menze, Klaus Maier-Hein, Spyridon Bakas

Faculty, Staff and Student Publications

Computational competitions are the standard for benchmarking medical image analysis algorithms, but they typically use small curated test datasets acquired at a few centers, leaving a gap to the reality of diverse multicentric patient data. To this end, the Federated Tumor Segmentation (FeTS) Challenge represents the paradigm for real-world algorithmic performance evaluation. The FeTS challenge is a competition to benchmark (i) federated learning aggregation algorithms and (ii) state-of-the-art segmentation algorithms, across multiple international sites. Weight aggregation and client selection techniques were compared using a multicentric brain tumor dataset in realistic federated learning simulations, yielding benefits for adaptive weight aggregation, and …

Breastfeeding Continuation At One Month Postpartum Among Women In Treatment For Opioid Use Disorder Who Initiated Breastfeeding: Prevalence And Determinants, Julia Eisenberg, Meghan Gannon, Kim Mclaughlin, Diane J. Abatemarco, Vanessa L. Short

Abington Jefferson Health Papers

Objective: To describe breastfeeding behaviors and determinants in the 1-month postdelivery period among women in treatment for opioid use disorder.

Study Design: Participants completed one questionnaire during pregnancy and one questionnaire at 1 month postpartum. Those who reported on the postpartum questionnaire that they had initiated breast- feeding were included in this analysis (N = 31). Infant feeding practices, receipt of lactation support, and demographic, psychosocial, and infant birth characteristics were compared between those who breastfed for at least 1 month and those who did not.

Results: In all, 45% of the participants were breastfeeding at 1 month post delivery. …

Rapid Access Chest Pain Assessment Clinic: An Australian Virtual Care Experience, Marwan Shawki, Thalys Sampaio Rodrigues, Hussein Al-Fiadh, Karen Sanders Mnursing, Ali H. Al-Fiadh

Journal of the Saudi Heart Association

Background: The Rapid Access Chest Pain Assessment Clinic (RACPAC) streamlines the evaluation of low to intermediate-risk chest pain patients, reducing hospitalisation and healthcare costs. However, there is limited data on the virtual model of care for RACPAC.

Aim: We sought to evaluate the structure, cost-effectiveness, and imaging modalities performance of face-to-face and virtual RACPAC in an Australian setting.

Methods:A retrospective analysis of patients attending the RACPAC within a large Australian quaternary hospital between 2012 and 2021. We described the clinic parameters and imaging modality utilisation with parametric and non-parametric descriptive statics. Patterns of diagnostic modality utilisation were assessed with …

Enhancing Diagnostic Reliability Through Centrifuge Validation And Staff Education: Quality Management Initiative In A Clinical Laboratory, Chris Agoki

MSMLS Capstone Projects

Abstract

This capstone project aims to enhance diagnostic reliability in a clinical laboratory by validating centrifuge performance and implementing an adult education-based training program within a quality management framework. Twenty archived, de-identified whole blood samples were analyzed to compare the performance of a new centrifuge with an existing model, focusing on plasma volume, hemolysis index, and Tacrolimus concentration.

The study demonstrated statistical and clinical equivalence between the devices, supporting the implementation of the new centrifuge. A staff training program, grounded in andragogical principles and guided by transformational leadership and Kotter’s 8-Step Change Model, was developed to integrate validation practices into …