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Utilization Of Suprathel® In Delayed Surgical Management Of Toxic Epidermal Necrolysis (Ten): A Case Report, Isabella Lipkin, Michelle Hughes, W. B. Hughes Md Feb 2025

Utilization Of Suprathel® In Delayed Surgical Management Of Toxic Epidermal Necrolysis (Ten): A Case Report, Isabella Lipkin, Michelle Hughes, W. B. Hughes Md

Jefferson Hospital Staff Papers and Presentations

Given the lack of established practice guidelines for the management of cutaneous symptoms associated with toxic epidermal necrolysis, treatments range from various dressings to skin substitutes. The following report details a case of a 21-year-old male patient with this diagnosis who presented nine days after rash eruption from an outside hospital with no signs of healing. The patient was then successfully managed surgically eleven days after symptom onset with debridement of epidermal blisters and placement of Suprathel®. To our knowledge, this publication is the first to describe the potential of this synthetic skin substitute in promoting epidermal regeneration for delayed …


Time To Initiation Of Antiresorptive Agents In Multiple Myeloma To Reduce Skeletal Related Events, Amman Bhasin, Adam Binder, Leland Damron, Amry Majeed, Adam Barsouk, Kelly Hughes, Thomas Jefferson University, Abdullateef O. Abdulkareem, Tingting Zhan, Divya Polu, Sai Gundepalli, Srinivas Devarakonda Feb 2025

Time To Initiation Of Antiresorptive Agents In Multiple Myeloma To Reduce Skeletal Related Events, Amman Bhasin, Adam Binder, Leland Damron, Amry Majeed, Adam Barsouk, Kelly Hughes, Thomas Jefferson University, Abdullateef O. Abdulkareem, Tingting Zhan, Divya Polu, Sai Gundepalli, Srinivas Devarakonda

Kimmel Cancer Center Faculty Papers

Purpose: Current treatment guidelines strongly support the use of antiresorptive therapy in patients with newly diagnosed multiple myeloma (NDMM) with the goal of preventing skeletal related events (SRE). Despite these concrete, data-driven recommendations, the impact of delays in antiresorptive initiation in NDMM patients is understudied. Through a multicenter retrospective study, we examined the impact of delays in antiresorptive initiation on the rates of SREs. We furthered our exploration of this topic in a separate retrospective analysis with a focus on reasons for delays in antiresorptive therapy initiation. Methods: Electronic health records from two large academic institutions were used to identify …


Pulmonopoly: A Game-Based Approach To Teach And Reinforce Basic Concepts Of Pulmonary Medicine To Medical Students, Michael Dong, James Uricheck, Urvashi Vaid Feb 2025

Pulmonopoly: A Game-Based Approach To Teach And Reinforce Basic Concepts Of Pulmonary Medicine To Medical Students, Michael Dong, James Uricheck, Urvashi Vaid

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

INTRODUCTION: Pulmonopoly is an innovative active-learning medical board game addressses core pulmonary concepts in an engaging, competitive style. The strength of Pulmonopoly lies in its ability to combine ease of setup and play with comprehensive content coverage that comprises a significant proportion of national board examinations, offering a gamification experience that can be readily applied in different settings and modified for learner levels.

METHODS: We created an instructional game, Pulmonopoly, based on pulmonary content delivered to preclinical medical students and required for national board examinations. We invited first-year medical students to participate in 60-minute small-group sessions. Content addressed pulmonary subject …


Multi-Societal Expert Consensus Statement On The Safe Administration Of Ultrasound Contrast Agents, Jordan B. Strom, Andrew Appis, Richard G. Barr, Maria Cristina Chammas, Dirk-André Clevert, Kassa Darge, Linda Feinstein, Steven B. Feinstein, J. Brian Fowlkes, Beverly Gorman, Pintong Huang, Yuko Kono, Juan Lopez-Mattei, Andrej Lyshchik, Michael L. Main, Wilson Matthias, Christina Merrill, Sharon L. Mulvagh, Petros Nihoyannopoulos, Joan Olson, Fabio Piscaglia, Thomas Porter, Arnaldo Rabischoffsky, Roxy Senior, Jessica L Stout, Maria Stanczak, Stephanie R. Wilson Feb 2025

Multi-Societal Expert Consensus Statement On The Safe Administration Of Ultrasound Contrast Agents, Jordan B. Strom, Andrew Appis, Richard G. Barr, Maria Cristina Chammas, Dirk-André Clevert, Kassa Darge, Linda Feinstein, Steven B. Feinstein, J. Brian Fowlkes, Beverly Gorman, Pintong Huang, Yuko Kono, Juan Lopez-Mattei, Andrej Lyshchik, Michael L. Main, Wilson Matthias, Christina Merrill, Sharon L. Mulvagh, Petros Nihoyannopoulos, Joan Olson, Fabio Piscaglia, Thomas Porter, Arnaldo Rabischoffsky, Roxy Senior, Jessica L Stout, Maria Stanczak, Stephanie R. Wilson

Department of Radiology Faculty Papers

Contrast enhanced ultrasound (CEUS) offers a safe, reliable imaging option to establish a clinical diagnosis across a variety of multidisciplinary settings. This Expert Consensus Statement serves to outline expert opinion on what constitutes appropriate supervision and the essential components of safe CEUS practice. The purpose of this document is to empower institutions to allow sonographers, along with other trained medical professionals, to administer UCAs at the point of care, consistent with the updated scope of practice documentation and within the broad parameters of an individual's training and licensure, while subject to appropriate supervision and meeting or exceeding minimum safety standards. …


The Mutational Landscape And Functional Effects Of Noncoding Ultraconserved Elements In Human Cancers, Recep Bayraktar, Yitao Tang, Mihnea P Dragomir, Cristina Ivan, Xinxin Peng, Linda Fabris, Jianhua Zhang, Alessandro Carugo, Serena Aneli, Jintan Liu, Mei-Ju M Chen, Sanjana Srinivasan, Iman Sahnoune, Emine Bayraktar, Kadir C Akdemir, Meng Chen, Pranav Narayanan, Wilson Huang, Leonie Florence Ott, Agda Karina Eterovic, Oscar Eduardo Villarreal, Mohammad Moustaf Mohammad, Michael D Peoples, Danielle M Walsh, Jon Andrew Hernandez, Margaret B Morgan, Kenna R Shaw, Jennifer S Davis, David Menter, Constantine S Tam, Paul Yeh, Sarah-Jane Dawson, Laura Z Rassenti, Thomas J Kipps, Tanja Kunej, Zeev Estrov, Simon A Joosse, Luca Pagani, Catherine Alix-Panabières, Klaus Pantel, Alessandra Ferajoli, Andrew Futreal, Ignacio I Wistuba, Milan Radovich, Scott Kopetz, Michael J Keating, Giulio F Draetta, John S Mattick, Han Liang, George A Calin Feb 2025

The Mutational Landscape And Functional Effects Of Noncoding Ultraconserved Elements In Human Cancers, Recep Bayraktar, Yitao Tang, Mihnea P Dragomir, Cristina Ivan, Xinxin Peng, Linda Fabris, Jianhua Zhang, Alessandro Carugo, Serena Aneli, Jintan Liu, Mei-Ju M Chen, Sanjana Srinivasan, Iman Sahnoune, Emine Bayraktar, Kadir C Akdemir, Meng Chen, Pranav Narayanan, Wilson Huang, Leonie Florence Ott, Agda Karina Eterovic, Oscar Eduardo Villarreal, Mohammad Moustaf Mohammad, Michael D Peoples, Danielle M Walsh, Jon Andrew Hernandez, Margaret B Morgan, Kenna R Shaw, Jennifer S Davis, David Menter, Constantine S Tam, Paul Yeh, Sarah-Jane Dawson, Laura Z Rassenti, Thomas J Kipps, Tanja Kunej, Zeev Estrov, Simon A Joosse, Luca Pagani, Catherine Alix-Panabières, Klaus Pantel, Alessandra Ferajoli, Andrew Futreal, Ignacio I Wistuba, Milan Radovich, Scott Kopetz, Michael J Keating, Giulio F Draetta, John S Mattick, Han Liang, George A Calin

Faculty, Staff and Student Publications

The mutational landscape of phylogenetically ultraconserved elements (UCEs), especially those in noncoding DNAs (ncUCEs), and their functional relevance in cancers remain poorly characterized. Here, we perform a systematic analysis of whole-genome and in-house targeted UCE sequencing datasets from more than 3000 patients with cancer of 13,736 UCEs and demonstrate that ncUCE somatic alterations are common. Using a multiplexed CRISPR knockout screen in colorectal cancer cells, we show that the loss of several altered ncUCEs significantly affects cell proliferation. In-depth functional studies in vitro and in vivo further reveal that specific ncUCEs can be enhancers of tumor suppressors (such as ARID1B) …


The Bacterial Microbiome Modulates The Initiation Of Brain Metastasis By Impacting The Gut-To-Brain Axis, Matteo Massara, Michelle Ballabio, Bastien Dolfi, Golnaz Morad, Vladimir Wischnewski, Eleni Lamprou, Joao Lourenco, Stéphanie Claudinot, Hector Gallart-Ayala, Rui Santalla Méndez, Annamaria Kauzlaric, Nadine Fournier, Ashish V Damania, Matthew C Wong, Julijana Ivanisevic, Nadim J Ajami, Jennifer A Wargo, Johanna A Joyce Feb 2025

The Bacterial Microbiome Modulates The Initiation Of Brain Metastasis By Impacting The Gut-To-Brain Axis, Matteo Massara, Michelle Ballabio, Bastien Dolfi, Golnaz Morad, Vladimir Wischnewski, Eleni Lamprou, Joao Lourenco, Stéphanie Claudinot, Hector Gallart-Ayala, Rui Santalla Méndez, Annamaria Kauzlaric, Nadine Fournier, Ashish V Damania, Matthew C Wong, Julijana Ivanisevic, Nadim J Ajami, Jennifer A Wargo, Johanna A Joyce

Faculty, Staff and Student Publications

Brain metastases (BrMs) are the most common brain tumors in patients and are associated with poor prognosis. Investigating the systemic and environmental factors regulating BrM biology represents an important strategy to develop effective treatments. Toward this goal, we explored the contribution of the gut microbiome to BrM development by using in vivo breast-BrM models under germ-free conditions or antibiotic treatment. This revealed a detrimental role of gut microbiota in fostering BrM initiation. We thus evaluated the impact of antibiotics and BrM outgrowth on the gut-brain axis. We found the bacterial genus Alistipes was differentially present under antibiotic treatment and BrM …


At-Home Stroke Neurorehabilitation: Early Findings With The Neuroexo Bci System, Juan José González-España, Lianne Sánchez-Rodríguez, Maxine Annel Pacheco-Ramírez, Jeff Feng, Kathryn Nedley, Shuo-Hsiu Chang, Gerard E Francisco, Jose L Contreras-Vidal Feb 2025

At-Home Stroke Neurorehabilitation: Early Findings With The Neuroexo Bci System, Juan José González-España, Lianne Sánchez-Rodríguez, Maxine Annel Pacheco-Ramírez, Jeff Feng, Kathryn Nedley, Shuo-Hsiu Chang, Gerard E Francisco, Jose L Contreras-Vidal

Faculty, Staff and Student Publications

Background: Democratized access to safe and effective robotic neurorehabilitation for stroke survivors requires innovative, affordable solutions that can be used not only in clinics but also at home. This requires the high usability of the devices involved to minimize costs associated with support from physical therapists or technicians.

Methods: This paper describes the early findings of the NeuroExo brain-machine interface (BMI) with an upper-limb robotic exoskeleton for stroke neurorehabilitation. This early feasibility study consisted of a six-week protocol, with an initial training and BMI calibration phase at the clinic followed by 60 sessions of neuromotor therapy at the homes of …


Immune Checkpoint Inhibitors Plus Debulking Surgery For Patients With Metastatic Renal Cell Carcinoma: Clinical Outcomes And Immunological Correlates Of A Prospective Pilot Trial, Sangeeta Goswami, Jianjun Gao, Sreyashi Basu, Daniel D Shapiro, Jose A Karam, Rebecca Slack Tidwell, Kamran Ahrar, Matthew T Campbell, Yu Shen, Alexandro E Trevino, Aaron T Mayer, Alexsandra B Espejo, Christian Seua, Marc D Macaluso, Yulong Chen, Wenbin Liu, Zhong He, Shalini S Yadav, Ying Wang, Priya Rao, Li Zhao, Jianhua Zhang, Sonali Jindal, Nizar M Tannir, Andrew Futreal, Linghua Wang, Padmanee Sharma Feb 2025

Immune Checkpoint Inhibitors Plus Debulking Surgery For Patients With Metastatic Renal Cell Carcinoma: Clinical Outcomes And Immunological Correlates Of A Prospective Pilot Trial, Sangeeta Goswami, Jianjun Gao, Sreyashi Basu, Daniel D Shapiro, Jose A Karam, Rebecca Slack Tidwell, Kamran Ahrar, Matthew T Campbell, Yu Shen, Alexandro E Trevino, Aaron T Mayer, Alexsandra B Espejo, Christian Seua, Marc D Macaluso, Yulong Chen, Wenbin Liu, Zhong He, Shalini S Yadav, Ying Wang, Priya Rao, Li Zhao, Jianhua Zhang, Sonali Jindal, Nizar M Tannir, Andrew Futreal, Linghua Wang, Padmanee Sharma

Faculty, Staff and Student Publications

Surgical removal of primary tumors reverses tumor-mediated immune suppression in pre-clinical models with metastatic disease. However, how cytoreductive surgery in the metastatic setting modulates the immune responses in patients, especially in the context of immune checkpoint therapy (ICT), is not understood. We report the first prospective, pilot, non-comparative clinical trial (NCT02210117) to evaluate the feasibility, clinical benefits, and immunologic changes of combining three different ICT-containing strategies with cytoreductive surgery or biopsy for patients with metastatic clear cell renal cell carcinoma. Primary safety endpoint of this trial has been met, with 43 patients completing cytoreductive surgery, 36 patients undergoing …


Pharmacological Interventions For Negative Symptoms In Schizophrenia: A Systematic Review Of Randomised Control Trials, Lorenzo Moccia, Francesca Bardi, Maria Benedetta Anesini, Sara Barbonetti, Georgios D Kotzalidis, Sara Rossi, Romina Caso, Flavia Grisoni, Giuseppe Mandracchia, Stella Margoni, Tommaso Callovini, Delfina Janiri, Marianna Mazza, Alessio Simonetti, Silvia Montanari, Gianna Autullo, Giovanni Camardese, Maria Pepe, Marco Di Nicola, Vassilij Di Giorgio, Fabio Conti, Gabriele Sani, On Behalf Of The Gemelli Repsy Study Group Feb 2025

Pharmacological Interventions For Negative Symptoms In Schizophrenia: A Systematic Review Of Randomised Control Trials, Lorenzo Moccia, Francesca Bardi, Maria Benedetta Anesini, Sara Barbonetti, Georgios D Kotzalidis, Sara Rossi, Romina Caso, Flavia Grisoni, Giuseppe Mandracchia, Stella Margoni, Tommaso Callovini, Delfina Janiri, Marianna Mazza, Alessio Simonetti, Silvia Montanari, Gianna Autullo, Giovanni Camardese, Maria Pepe, Marco Di Nicola, Vassilij Di Giorgio, Fabio Conti, Gabriele Sani, On Behalf Of The Gemelli Repsy Study Group

Faculty, Staff and Students Publications

Background/Objectives: While positive symptoms of schizophrenia are often satisfactorily controlled, negative symptoms are difficult to treat, persisting despite treatment. Different strategies have been devised to deal with this problem. We aimed to review drug treatment for negative symptoms of schizophrenia in controlled trials of marketed drugs.

Methods: We searched the PubMed database and the resulting records' reference lists to identify eligible trials using schizophrenia[ti] AND "negative symptom*"[ti] as a search strategy. We determined eligibility through Delphi rounds among all authors.

Results: On 11 February 2025, we identified 1485 records on PubMed and 3 more from reference lists. Eligible were 95 …


Neural Signal Analysis In Chronic Stroke: Advancing Intracortical Brain-Computer Interface Design, Nabila Shawki, Alessandro Naopli, Carlos E. Vargas-Irwin, Christopher K. Thompson, John P. Donoghue, Mijail D. Serruya Feb 2025

Neural Signal Analysis In Chronic Stroke: Advancing Intracortical Brain-Computer Interface Design, Nabila Shawki, Alessandro Naopli, Carlos E. Vargas-Irwin, Christopher K. Thompson, John P. Donoghue, Mijail D. Serruya

Department of Medicine Faculty Papers

INTRODUCTION: Intracortical Brain-computer interfaces (iBCIs) are a promising technology to restore function after stroke. It remains unclear whether iBCIs will be able to use the signals available in the neocortex overlying stroke affecting the underlying white matter and basal ganglia.

METHODS: Here, we decoded both local field potentials (LFPs) and spikes recorded from intracortical electrode arrays in a person with chronic cerebral subcortical stroke performing various tasks with his paretic hand, with and without a powered orthosis. Analysis of these neural signals provides an opportunity to explore the electrophysiological activities of a stroke affected brain and inform the design of …


Characterization Of Rationally Designed Crispr/Cas9-Based Dna Methyltransferases With Distinct Methyltransferase And Gene Silencing Activities In Human Cell Lines And Primary Human T Cells, Rosa Selenia Guerra-Resendez, Samantha Legoff Lydon, Alex J Ma, Guy C Bedford, Daniel R Reed, Sunghwan Kim, Erik R Terán, Tomoki Nishiguchi, Mario Escobar, Andrew R Dinardo, Isaac B Hilton Feb 2025

Characterization Of Rationally Designed Crispr/Cas9-Based Dna Methyltransferases With Distinct Methyltransferase And Gene Silencing Activities In Human Cell Lines And Primary Human T Cells, Rosa Selenia Guerra-Resendez, Samantha Legoff Lydon, Alex J Ma, Guy C Bedford, Daniel R Reed, Sunghwan Kim, Erik R Terán, Tomoki Nishiguchi, Mario Escobar, Andrew R Dinardo, Isaac B Hilton

Faculty, Staff and Students Publications

Nuclease-deactivated Cas (dCas) proteins can be used to recruit epigenetic effectors, and this class of epigenetic editing technologies has revolutionized the ability to synthetically control the mammalian epigenome and transcriptome. DNA methylation is one of the most important and well-characterized epigenetic modifications in mammals, and while many different forms of dCas-based DNA methyltransferases (dCas-DNMTs) have been developed for programmable DNA methylation, these tools are frequently poorly tolerated and/or lowly expressed in mammalian cell types. Further, the use of dCas-DNMTs has largely been restricted to cell lines, which limits mechanistic insights in karyotypically normal contexts and hampers translational utility in the …


Invasion And Metastasis In Cancer: Molecular Insights And Therapeutic Targets, Yongxing Li, Fengshuo Liu, Qingjin Cai, Lijun Deng, Qin Ouyang, Xiang H-F Zhang, Ji Zheng Feb 2025

Invasion And Metastasis In Cancer: Molecular Insights And Therapeutic Targets, Yongxing Li, Fengshuo Liu, Qingjin Cai, Lijun Deng, Qin Ouyang, Xiang H-F Zhang, Ji Zheng

Faculty, Staff and Students Publications

The progression of malignant tumors leads to the development of secondary tumors in various organs, including bones, the brain, liver, and lungs. This metastatic process severely impacts the prognosis of patients, significantly affecting their quality of life and survival rates. Research efforts have consistently focused on the intricate mechanisms underlying this process and the corresponding clinical management strategies. Consequently, a comprehensive understanding of the biological foundations of tumor metastasis, identification of pivotal signaling pathways, and systematic evaluation of existing and emerging therapeutic strategies are paramount to enhancing the overall diagnostic and treatment capabilities for metastatic tumors. However, current research is …


Empowering Resident Autonomy, Competence, And Relatedness Through Opt-Out Visits, Emily Lisco, Md, Alexandra Hughes, Lcsw, Meghan O’Meara, Phd, Lpc Feb 2025

Empowering Resident Autonomy, Competence, And Relatedness Through Opt-Out Visits, Emily Lisco, Md, Alexandra Hughes, Lcsw, Meghan O’Meara, Phd, Lpc

Department of Psychiatry and Human Behavior Posters

Background

  • House staff officers are more likely to experience burnout than their age-matched peers in the general population.3
  • ACGME Common Program requirements emphasize the importance of well-being in residency programs, including the opportunity to attend healthcare appointments during working hours.1
  • Opt-out programs have been used to increase help-seeking behavior and provide low-barrier access to mental health care and other supports.2, 4-5
  • Self-determination theory proposes that individuals’ well-being can be enhanced if the core psychological needs of autonomy, competence, and relatedness are met.6
  • The lack of perceived autonomy, competence, and connection felt by residents can lead to …


Automated Detection Of Reduced Ejection Fraction Using An Ecg-Enabled Digital Stethoscope: A Large Cohort Validation, Ling Guo, Gregg S. Pressman, Spencer N. Kieu, Scott B. Marrus, George Mathew, John Prince, Emileigh Lastowski, Rosalie V. Mcdonough, Caroline Currie, John N. Maidens, Hussein Al-Sudani, Evan Friend, Deepak Padmanabhan, Preetham Kumar, Edward Kersh, Subramaniam Venkatraman, Salima Qamruddin Feb 2025

Automated Detection Of Reduced Ejection Fraction Using An Ecg-Enabled Digital Stethoscope: A Large Cohort Validation, Ling Guo, Gregg S. Pressman, Spencer N. Kieu, Scott B. Marrus, George Mathew, John Prince, Emileigh Lastowski, Rosalie V. Mcdonough, Caroline Currie, John N. Maidens, Hussein Al-Sudani, Evan Friend, Deepak Padmanabhan, Preetham Kumar, Edward Kersh, Subramaniam Venkatraman, Salima Qamruddin

Einstein Health Papers

BACKGROUND: Asymptomatic left ventricular systolic dysfunction (ALVSD) affects 7 million globally, leading to delayed diagnosis and treatment, high mortality, and substantial downstream health care costs. Current detection methods for ALVSD are inadequate, necessitating the development of improved diagnostic tools. Recently, electrocardiogram-based algorithms have shown promise in detecting ALVSD.

OBJECTIVES: The authors developed and validated a convolutional neural network (CNN) model using single-lead electrocardiogram and phonocardiogram inputs captured by a digital stethoscope to assess its utility in detecting individuals with actionably low ejection fractions (EF) in a large cohort of patients.

METHODS: 2,960 adults undergoing echocardiography from 4 U.S. health care …


Erythritol, Erythronate, And Cardiovascular Outcomes In Older Adults In The Aric Study, Layla A Abushamat, Bing Yu, Ron C Hoogeveen, Caroline Sun, Chao Cheng, Sean M Hartig, Mark A Herman, Ashok Balasubramanyam, Jane Eb Reusch, Elizabeth Selvin, Chiadi E Ndumele, Vijay Nambi, Christie M Ballantyne Feb 2025

Erythritol, Erythronate, And Cardiovascular Outcomes In Older Adults In The Aric Study, Layla A Abushamat, Bing Yu, Ron C Hoogeveen, Caroline Sun, Chao Cheng, Sean M Hartig, Mark A Herman, Ashok Balasubramanyam, Jane Eb Reusch, Elizabeth Selvin, Chiadi E Ndumele, Vijay Nambi, Christie M Ballantyne

Faculty, Staff and Student Publications

BACKGROUND: Circulating erythritol, an endogenously produced metabolite and an artificial sweetener, is associated with cardiovascular outcomes.

OBJECTIVES: The authors assessed associations of erythritol and its downstream metabolite, erythronate, with cardiovascular risk factors and events in older adults in the ARIC (Atherosclerosis Risk In Communities) study (visit 5, 2011-2013).

METHODS: We included 4,006 participants without prevalent cardiovascular disease and with metabolomic profiling. Erythritol and erythronate were measured by mass spectrometry. We analyzed associations of log-transformed erythritol and erythronate with cardiovascular risk factors and events using Cox proportional hazard models.

RESULTS: Participants in the highest tertiles of erythritol or erythronate were older, …


Semaglutide And Nonarteritic Anterior Ischemic Optic Neuropathy, Cindy X Cai, Michelle Hribar, Sally Baxter, Kerry Goetz, Swarup S Swaminathan, Alexis Flowers, Eric N Brown, Brian Toy, Benjamin Xu, John Chen, Aiyin Chen, Sophia Wang, Cecilia Lee, Theodore Leng, Joshua R Ehrlich, Andrew Barkmeier, Karen R Armbrust, Michael V Boland, David Dorr, Danielle Boyce, Thamir Alshammari, Joel Swerdel, Marc A Suchard, Martijn Schuemie, Fan Bu, Anthony G Sena, George Hripcsak, Akihiko Nishimura, Paul Nagy, Thomas Falconer, Scott L Duvall, Michael Matheny, Benjamin Viernes, William O'Brien, Linying Zhang, Benjamin Martin, Erik Westlund, Nestoras Mathioudakis, Ruochong Fan, Adam Wilcox, Albert Lai, Jacqueline C Stocking, Sahar Takkouche, Lok Hin Lee, Yangyiran Xie, Izabelle Humes, David B Mccoy, Mohammad Adibuzzaman, Raymond G Areaux, William Rojas-Carabali, James Brash, David A Lee, Nicole G Weiskopf, Louise Mawn, Rupesh Agrawal, Hannah Morgan-Cooper, Priya Desai, Patrick B Ryan Feb 2025

Semaglutide And Nonarteritic Anterior Ischemic Optic Neuropathy, Cindy X Cai, Michelle Hribar, Sally Baxter, Kerry Goetz, Swarup S Swaminathan, Alexis Flowers, Eric N Brown, Brian Toy, Benjamin Xu, John Chen, Aiyin Chen, Sophia Wang, Cecilia Lee, Theodore Leng, Joshua R Ehrlich, Andrew Barkmeier, Karen R Armbrust, Michael V Boland, David Dorr, Danielle Boyce, Thamir Alshammari, Joel Swerdel, Marc A Suchard, Martijn Schuemie, Fan Bu, Anthony G Sena, George Hripcsak, Akihiko Nishimura, Paul Nagy, Thomas Falconer, Scott L Duvall, Michael Matheny, Benjamin Viernes, William O'Brien, Linying Zhang, Benjamin Martin, Erik Westlund, Nestoras Mathioudakis, Ruochong Fan, Adam Wilcox, Albert Lai, Jacqueline C Stocking, Sahar Takkouche, Lok Hin Lee, Yangyiran Xie, Izabelle Humes, David B Mccoy, Mohammad Adibuzzaman, Raymond G Areaux, William Rojas-Carabali, James Brash, David A Lee, Nicole G Weiskopf, Louise Mawn, Rupesh Agrawal, Hannah Morgan-Cooper, Priya Desai, Patrick B Ryan

Faculty, Staff and Student Publications

Importance

Semaglutide, a glucagonlike peptide-1 receptor agonist (GLP-1RA), has recently been implicated in cases of nonarteritic anterior ischemic optic neuropathy (NAION), raising safety concerns in the treatment of type 2 diabetes (T2D).

Objective

To investigate the potential association between semaglutide and NAION in the Observational Health Data Sciences and Informatics (OHDSI) network.

Design, Setting, and Participants

This was a retrospective study across 14 databases (6 administrative claims and 8 electronic health records). Included were adults with T2D taking semaglutide, other GLP-1RA (dulaglutide, exenatide), or non–GLP-1RA medications (empagliflozin, sitagliptin, glipizide) from December 1, 2017, to December 31, 2023. The incidence proportion …


Antibiotic-Induced Loss Of Gut Microbiome Metabolic Output Correlates With Clinical Responses To Car T-Cell Therapy, Rishika Prasad, Abdur Rehman, Lubna Rehman, Faezeh Darbaniyan, Viktoria Blumenberg, Maria-Luisa Schubert, Uria Mor, Eli Zamir, Sabine Schmidt, Tomo Hayase, Chia-Chi Chang, Lauren Mcdaniel, Ivonne Flores, Paolo Strati, Ranjit Nair, Dai Chihara, Luis E Fayad, Sairah Ahmed, Swaminathan P Iyer, Michael Wang, Preetesh Jain, Loretta J Nastoupil, Jason Westin, Reetakshi Arora, Joel Turner, Fareed Khawaja, Ranran Wu, Jennifer B Dennison, Meghan Menges, Melanie Hidalgo-Vargas, Kayla Reid, Marco L Davila, Peter Dreger, Felix Korell, Anita Schmitt, Mark R Tanner, Richard E Champlin, Christopher R Flowers, Elizabeth J Shpall, Samir Hanash, Sattva S Neelapu, Michael Schmitt, Marion Subklewe, Johannes Francois-Fahrmann, C K Stein-Thoeringer, Eran Elinav, Michael D Jain, Eiko Hayase, Robert R Jenq, Neeraj Y Saini Feb 2025

Antibiotic-Induced Loss Of Gut Microbiome Metabolic Output Correlates With Clinical Responses To Car T-Cell Therapy, Rishika Prasad, Abdur Rehman, Lubna Rehman, Faezeh Darbaniyan, Viktoria Blumenberg, Maria-Luisa Schubert, Uria Mor, Eli Zamir, Sabine Schmidt, Tomo Hayase, Chia-Chi Chang, Lauren Mcdaniel, Ivonne Flores, Paolo Strati, Ranjit Nair, Dai Chihara, Luis E Fayad, Sairah Ahmed, Swaminathan P Iyer, Michael Wang, Preetesh Jain, Loretta J Nastoupil, Jason Westin, Reetakshi Arora, Joel Turner, Fareed Khawaja, Ranran Wu, Jennifer B Dennison, Meghan Menges, Melanie Hidalgo-Vargas, Kayla Reid, Marco L Davila, Peter Dreger, Felix Korell, Anita Schmitt, Mark R Tanner, Richard E Champlin, Christopher R Flowers, Elizabeth J Shpall, Samir Hanash, Sattva S Neelapu, Michael Schmitt, Marion Subklewe, Johannes Francois-Fahrmann, C K Stein-Thoeringer, Eran Elinav, Michael D Jain, Eiko Hayase, Robert R Jenq, Neeraj Y Saini

Faculty, Staff and Student Publications

Antibiotic (ABX)–induced microbiome dysbiosis is widespread in oncology, adversely affecting outcomes and side effects of various cancer treatments, including immune checkpoint inhibitors and chimeric antigen receptor T-cell (CAR-T) therapies. In this study, we observed that prior exposure to broad-spectrum ABXs with extended anaerobic coverage such as piperacillin-tazobactam and meropenem was associated with worse anti-CD19 CAR-T therapy survival outcomes in patients with large B-cell lymphoma (N = 422) than other ABX classes. In a discovery subset of these patients (n = 67), we found that the use of these ABXs was in turn associated with substantial dysbiosis of gut microbiome function, …


Aif3 Splicing Variant Elicits Mitochondrial Malfunction Via The Concurrent Dysregulation Of Electron Transport Chain And Glutathione-Redox Homeostasis, Mi Zhou, Shuiqiao Liu, Yanan Wang, Bo Zhang, Ming Zhu, Jennifer E Wang, Veena Rajaram, Yisheng Fang, Weibo Luo, Yingfei Wang Feb 2025

Aif3 Splicing Variant Elicits Mitochondrial Malfunction Via The Concurrent Dysregulation Of Electron Transport Chain And Glutathione-Redox Homeostasis, Mi Zhou, Shuiqiao Liu, Yanan Wang, Bo Zhang, Ming Zhu, Jennifer E Wang, Veena Rajaram, Yisheng Fang, Weibo Luo, Yingfei Wang

Faculty, Staff and Student Publications

Genetic mutations in apoptosis-inducing factor (AIF) have a strong association with mitochondrial disorders; however, little is known about the aberrant splicing variants in affected patients and how these variants contribute to mitochondrial dysfunction and brain development defects. We identified pathologic AIF3/AIF3-like splicing variants in postmortem brain tissues of pediatric individuals with mitochondrial disorders. Mutations in AIFM1 exon-2/3 increase splicing risks. AIF3-splicing disrupts mitochondrial complexes, membrane potential, and respiration, causing brain development defects. Mechanistically, AIF is a mammalian NAD(P)H dehydrogenase and possesses glutathione reductase activity controlling respiratory chain functions and glutathione regeneration. Conversely, AIF3, lacking these activities, disassembles mitochondrial complexes, increases …


A Protocol To Purify Human Mediator Complex From Freestyle 293-F Cells, Hui-Chi Tang, Kuang-Lei Tsai, Ti-Chun Chao Feb 2025

A Protocol To Purify Human Mediator Complex From Freestyle 293-F Cells, Hui-Chi Tang, Kuang-Lei Tsai, Ti-Chun Chao

Faculty, Staff and Student Publications

The Mediator, a multi-subunit protein complex in all eukaryotes, comprises the core mediator (cMED) and the CDK8 kinase module (CKM). As a molecular bridge between transcription factors (TFs) and RNA polymerase II (Pol II), the Mediator plays a critical role in regulating Pol II-dependent transcription. Considering its large size and complex composition, conducting in vitro studies on the Mediator complex is challenging, especially when isolating the intact and homogeneous complex from human cells. Here, we present a method to purify the intact CKM-cMED complex from FreeStyle 293-F cells (293-F cells), which offers advantages for performing large-scale protein purification. To isolate …


Membrane Lipids Augment Cell Envelope Stress Signaling Via The Madrs System To Defend Against Antimicrobial Peptides And Antibiotics In Enterococcus Faecalis, William R Miller, April Nguyen, Kavindra V Singh, Samie Rizvi, Ayesha Khan, Sam G Erickson, Stephanie L Egge, Melissa Cruz, An Q Dinh, Lorena Diaz, Philip C Thornton, Rutan Zhang, Libin Xu, Danielle A Garsin, Yousif Shamoo, Cesar A Arias Feb 2025

Membrane Lipids Augment Cell Envelope Stress Signaling Via The Madrs System To Defend Against Antimicrobial Peptides And Antibiotics In Enterococcus Faecalis, William R Miller, April Nguyen, Kavindra V Singh, Samie Rizvi, Ayesha Khan, Sam G Erickson, Stephanie L Egge, Melissa Cruz, An Q Dinh, Lorena Diaz, Philip C Thornton, Rutan Zhang, Libin Xu, Danielle A Garsin, Yousif Shamoo, Cesar A Arias

Faculty, Staff and Student Publications

Enterococci have evolved resistance mechanisms to protect their cell envelopes against bacteriocins and host cationic antimicrobial peptides (CAMPs) produced in the gastrointestinal environment. Activation of the membrane stress response has also been tied to resistance to the lipopeptide antibiotic daptomycin. However, the actual effectors mediating resistance have not been elucidated. Here, we show that the MadRS (formerly YxdJK) membrane antimicrobial peptide defense system controls a network of genes, including a previously uncharacterized 3-gene operon (madEFG) that protects the Enterococcus faecalis cell envelope from antimicrobial peptides. Constitutive activation of the system confers protection against CAMPs and daptomycin in the absence of …


Zika Virus Ns1 Drives Tunneling Nanotube Formation For Mitochondrial Transfer And Stealth Transmission In Trophoblasts, Rafael T Michita, Long B Tran, Steven J Bark, Deepak Kumar, Shay A Toner, Joyce Jose, Indira U Mysorekar, Anoop Narayanan Feb 2025

Zika Virus Ns1 Drives Tunneling Nanotube Formation For Mitochondrial Transfer And Stealth Transmission In Trophoblasts, Rafael T Michita, Long B Tran, Steven J Bark, Deepak Kumar, Shay A Toner, Joyce Jose, Indira U Mysorekar, Anoop Narayanan

Faculty, Staff and Students Publications

Zika virus (ZIKV) is unique among orthoflaviviruses in its vertical transmission capacity in humans, yet the underlying mechanisms remain incompletely understood. Here, we show that ZIKV induces tunneling nanotubes (TNTs) in placental trophoblasts which facilitate transfer of viral particles, proteins, mitochondria, and RNA to neighboring uninfected cells. TNT formation is driven exclusively via ZIKV non-structural protein 1 (NS1). Specifically, the N-terminal 1-50 amino acids of membrane-bound ZIKV NS1 are necessary for triggering TNT formation in host cells. Trophoblasts infected with TNT-deficient ZIKV


Oral Inflammation And Microbiome Dysbiosis Exacerbate Chronic Graft-Versus-Host Disease, Yui Kambara, Hideaki Fujiwara, Akira Yamamoto, Kazuyoshi Gotoh, Shuma Tsuji, Mari Kunihiro, Tadashi Oyama, Toshiki Terao, Ayame Sato, Takehiro Tanaka, Daniel Peltier, Keisuke Seike, Hisakazu Nishimori, Noboru Asada, Daisuke Ennishi, Keiko Fujii, Nobuharu Fujii, Ken-Ichi Matsuoka, Yoshihiko Soga, Pavan Reddy, Yoshinobu Maeda Feb 2025

Oral Inflammation And Microbiome Dysbiosis Exacerbate Chronic Graft-Versus-Host Disease, Yui Kambara, Hideaki Fujiwara, Akira Yamamoto, Kazuyoshi Gotoh, Shuma Tsuji, Mari Kunihiro, Tadashi Oyama, Toshiki Terao, Ayame Sato, Takehiro Tanaka, Daniel Peltier, Keisuke Seike, Hisakazu Nishimori, Noboru Asada, Daisuke Ennishi, Keiko Fujii, Nobuharu Fujii, Ken-Ichi Matsuoka, Yoshihiko Soga, Pavan Reddy, Yoshinobu Maeda

Faculty, Staff and Students Publications

The oral microbiota, second in abundance to the gut, is implicated in chronic systemic diseases, but its specific role in graft-versus-host disease (GVHD) pathogenesis has been unclear. Our study finds that mucositis-induced oral dysbiosis in patients after hematopoietic cell transplantation (HCT) associated with increased chronic GVHD (cGVHD), even in patients receiving posttransplant cyclophosphamide. In murine HCT models, oral dysbiosis caused by bilateral molar ligatures exacerbated cGVHD and increased bacterial load in the oral cavity and gut, with Enterococcaceae significantly increasing in both organs. In this model, the migration of Enterococcaceae to cervical lymph nodes both before and after transplantation activated …


Does Adiponectin Inform Cardiovascular Risk In Older Adults?: The Aric Study, Layla A Abushamat, Xiaoming Jia, Lu Xu, Chao Cheng, Chiadi E Ndumele, Caroline Sun, B Gwen Windham, Kunihiro Matsushita, Bing Yu, Vijay Nambi, Biykem Bozkurt, Jane E B Reusch, Casey M Rebholz, Elizabeth Selvin, Christie M Ballantyne, Ron C Hoogeveen Feb 2025

Does Adiponectin Inform Cardiovascular Risk In Older Adults?: The Aric Study, Layla A Abushamat, Xiaoming Jia, Lu Xu, Chao Cheng, Chiadi E Ndumele, Caroline Sun, B Gwen Windham, Kunihiro Matsushita, Bing Yu, Vijay Nambi, Biykem Bozkurt, Jane E B Reusch, Casey M Rebholz, Elizabeth Selvin, Christie M Ballantyne, Ron C Hoogeveen

Faculty, Staff and Student Publications

BACKGROUND: Adiponectin, an atheroprotective adipokine, is associated with adverse outcomes in older age. It is unclear whether this is due to overlapping pathophysiological pathways with N-terminal pro-B-type natriuretic peptide (NT-proBNP).

OBJECTIVES: The authors investigated adiponectin's associations with cardiovascular disease (CVD) risk in older adults.

METHODS: Among Atherosclerosis Risk in Communities prospective cohort study participants without baseline CVD at visit 5 (n = 4,729, mean age 75), adiponectin and adiponectin/NT-proBNP category associations with incident CVD events (heart failure [HF], atherosclerotic cardiovascular disease, and death during median follow-up of 5.5 years) and echocardiographic parameters were assessed. Metabolomic signatures of adiponectin/NT-proBNP categories were …


Ischemia And Anatomy In The New 2024 European Guidelines For Chronic Coronary Syndromes: Update And Comparison Of Recommendations, Christian Adrián Caroli Feb 2025

Ischemia And Anatomy In The New 2024 European Guidelines For Chronic Coronary Syndromes: Update And Comparison Of Recommendations, Christian Adrián Caroli

Journal of the Saudi Heart Association

The new 2024 European guideline on chronic coronary syndromes is a pivotal document for clinical practice, updating the evidence and indications after five years, incorporating insights from the paradigm-shifting ISCHEMIA trial. This article explores the evolving role of functional and anatomical testing in assessing coronary artery disease, highlighting the introduction of a new risk probability score based on clinical and risk factors. Additionally, it provides a detailed comparison between these European recommendations and those from the most influential American guidelines, emphasizing key differences in the approach to risk stratification and diagnostic strategies. This comprehensive analysis provides valuable insights for optimizing …


Intraocular Pressure Changes Associated With Psychological Stress Or Anxiety In Both Healthy And Glaucoma-Diagnosed Patients, Triston Crook, Porter Biggs, James Fini, Zane Kingsbury Feb 2025

Intraocular Pressure Changes Associated With Psychological Stress Or Anxiety In Both Healthy And Glaucoma-Diagnosed Patients, Triston Crook, Porter Biggs, James Fini, Zane Kingsbury

Annual Research Symposium

No abstract provided.


Retrospective Analysis Of Angiotensin Receptor Blockers And Knee Cartilage Volume In Osteoarthritis: Evidence From The Osteoarthritis Initiative, Parv Kale, Vijay Kale Feb 2025

Retrospective Analysis Of Angiotensin Receptor Blockers And Knee Cartilage Volume In Osteoarthritis: Evidence From The Osteoarthritis Initiative, Parv Kale, Vijay Kale

Annual Research Symposium

No abstract provided.


Takotsubo Cardiomyopathy: A Case Of The Broken Heart, Lilian Huynh, Kaylee Putney Feb 2025

Takotsubo Cardiomyopathy: A Case Of The Broken Heart, Lilian Huynh, Kaylee Putney

Annual Research Symposium

Takotsubo cardiomyopathy (TC), or "broken heart syndrome," is a rare cardiac condition causing temporary left ventricular dysfunction due to severe stress. Though the exact cause is unclear, it mimics myocardial infarction and can lead to cardiogenic shock. Current treatment lacks specific guidelines and relies on heart failure protocols. We report a case of a patient with TC-induced cardiogenic shock, likely triggered by emotional stress. She required vasopressors, a percutaneous intervention, an Impella device, and guideline-directed medication therapies. This case underscores the significance of establishing guideline optimizations for managing TC and cardiogenic shock.


Evaluation Of Seven Commercially Available Dna Extraction Kits For Ocular Tissues, Jakob Newton, Conrad K. Ashby, Michael Trapnell, Triston Crook, Mark Eisele, Porter Biggs, Prina Patel, Christina Nelson, John A. Kriak, Kyle B. Bills, David W. Sant Feb 2025

Evaluation Of Seven Commercially Available Dna Extraction Kits For Ocular Tissues, Jakob Newton, Conrad K. Ashby, Michael Trapnell, Triston Crook, Mark Eisele, Porter Biggs, Prina Patel, Christina Nelson, John A. Kriak, Kyle B. Bills, David W. Sant

Annual Research Symposium

2025 Annual Roseman Research Symposium


Correlation Of Gnas Mutational Status With Oncologic Outcomes In Patients With Resected Intraductal Papillary Mucinous Neoplasms, Julia S. Evans, Kylee Shivok, Hui Hsuan Chen, Eliyahu Gorgov, Wilbur Bowne, Aditi Jain, Phd, Harish Lavu, Charles J. Yeo, Avinoam Nevler Feb 2025

Correlation Of Gnas Mutational Status With Oncologic Outcomes In Patients With Resected Intraductal Papillary Mucinous Neoplasms, Julia S. Evans, Kylee Shivok, Hui Hsuan Chen, Eliyahu Gorgov, Wilbur Bowne, Aditi Jain, Phd, Harish Lavu, Charles J. Yeo, Avinoam Nevler

SKMC Student Presentations and Publications

Background: Intraductal papillary mucinous neoplasms (IPMNs) are pre-malignant pancreatic lesions that may progress to invasive pancreatic ductal adenocarcinoma (PDAC). IPMN-associated invasive carcinoma (iIPMN) has been associated with more favorable survival outcomes compared to non-iIPMN-derived PDAC. Here, we aim to investigate the genetic landscape of IPMNs to assess their relevance to oncologic outcomes. Methods: This retrospective study used a large single-institution prospectively maintained database. Patients who underwent curative-intent pancreatic resection between 2016 and 2022 with histologically confirmed diagnosis of IPMN were included. Demographic, pathologic, molecular, and oncologic outcome data were recorded. Kaplan–Meier survival analyses were performed. PDAC data from public genetic …


Development Of A Conditional Plasmid For Gene Deletion In Non-Model Fusobacterium Nucleatum Strains, Peng Zhou, Bibek G C, Chenggang Wu Feb 2025

Development Of A Conditional Plasmid For Gene Deletion In Non-Model Fusobacterium Nucleatum Strains, Peng Zhou, Bibek G C, Chenggang Wu

Faculty, Staff and Student Publications

Fusobacterium nucleatum is an opportunistic pathogen with four subspecies: nucleatum (FNN), vincentii (FNV), polymorphum (FNP), and animalis (FNA), each with distinct disease potentials. Research on fusobacterial pathogenesis has mainly focused on the model strain ATCC 23726 from FNN. However, this narrow focus may overlook significant behaviors of other FNN strains and those from other subspecies, given the genetic and phenotypic diversity within F. nucleatum. While ATCC 23726 is highly transformable, most other Fusobacterium strains exhibit low transformation efficiency, complicating traditional gene deletion methods that rely on non-replicating plasmids. To address this, we developed a conditional plasmid system in which …