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2023

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Articles 2611 - 2640 of 9373

Full-Text Articles in Medical Specialties

The Combination Of Platelet Rich Plasma And Corticosteroids In Musculoskeletal And Musculotendinous Pathologies, Mikayla Stoudt Aug 2023

The Combination Of Platelet Rich Plasma And Corticosteroids In Musculoskeletal And Musculotendinous Pathologies, Mikayla Stoudt

Master of Science in Physician Assistant Studies Capstone Presentations (Center City)

Background

- 126 million Americans reported to have a musculoskeletal or musculotendinous pathology in 20121

- Combined direct and indirect cost of these injuries in 2015 was $874 billion1

- Corticosteroid injections have been the mainstay of invasive management after conservative methods fail
Long-term effects of corticosteroids

  • Intra-articular injections for knee osteoarthritis resulted in cartilage volume loss10
  • Harm to flexor tendons, neurovascular structures, and compromised integrity7, 11

- Platelet Rich Plasma

  • Sample patient blood --> Centrifuge --> Separate plasma and platelets from other blood products --> Reconcentrate the platelets into the plasma
  • Platelets release growth factor …


Labeling Piezo2 Activity In The Peripheral Nervous System, Nicholas W Villarino, Yasmeen M F Hamed, Britya Ghosh, Adrienne E Dubin, Amanda H Lewis, Max A Odem, Meaghan C Loud, Yu Wang, M Rocio Servin-Vences, Ardem Patapoutian, Kara L Marshall Aug 2023

Labeling Piezo2 Activity In The Peripheral Nervous System, Nicholas W Villarino, Yasmeen M F Hamed, Britya Ghosh, Adrienne E Dubin, Amanda H Lewis, Max A Odem, Meaghan C Loud, Yu Wang, M Rocio Servin-Vences, Ardem Patapoutian, Kara L Marshall

Duncan NRI Faculty and Staff Publications

Sensory neurons detect mechanical forces from both the environment and internal organs to regulate physiology. PIEZO2 is a mechanosensory ion channel critical for touch, proprioception, and bladder stretch sensation, yet its broad expression in sensory neurons suggests it has undiscovered physiological roles. To fully understand mechanosensory physiology, we must know where and when PIEZO2-expressing neurons detect force. The fluorescent styryl dye FM 1-43 was previously shown to label sensory neurons. Surprisingly, we find that the vast majority of FM 1-43 somatosensory neuron labeling in mice in vivo is dependent on PIEZO2 activity within the peripheral nerve endings. We illustrate the …


Enhanced Cerebroprotection Of Xenon-Loaded Liposomes In Combination With Rtpa Thrombolysis For Embolic Ischemic Stroke, Tao Peng, Keith Booher, Melanie R Moody, Xing Yin, Jaroslaw Aronowski, David D Mcpherson, Sean I Savitz, Hyunggun Kim, Shao-Ling Huang Aug 2023

Enhanced Cerebroprotection Of Xenon-Loaded Liposomes In Combination With Rtpa Thrombolysis For Embolic Ischemic Stroke, Tao Peng, Keith Booher, Melanie R Moody, Xing Yin, Jaroslaw Aronowski, David D Mcpherson, Sean I Savitz, Hyunggun Kim, Shao-Ling Huang

Faculty, Staff and Student Publications

Xenon (Xe) has shown great potential as a stroke treatment due to its exceptional ability to protect brain tissue without inducing side effects. We have previously developed Xe-loaded liposomes for the ultrasound-activated delivery of Xe into the cerebral region and demonstrated their therapeutic efficacy. At present, the sole FDA-approved thrombolytic agent for stroke treatment is recombinant tissue plasminogen activator (rtPA). In this study, we aimed to investigate the potential of combining Xe-liposomes with an intravenous rtPA treatment in a clinically relevant embolic rat stroke model. We evaluated the combinational effect using an in vitro clot lysis model and an in …


Dosimetric Evaluation Of Left-Sided Chest Wall Vmat Treatment With And Without Jaw Tracking; Dose Comparison Of Left Anterior Descending Artery Versus Heart Mean Dose, Jacqueline J. Emus Aug 2023

Dosimetric Evaluation Of Left-Sided Chest Wall Vmat Treatment With And Without Jaw Tracking; Dose Comparison Of Left Anterior Descending Artery Versus Heart Mean Dose, Jacqueline J. Emus

Masters Projects

Radiation therapy has significantly improved breast cancer survival rates; however, it can still lead to long-term side effects, particularly affecting the heart. Left-side breast cancer patients face higher risks due to the proximity of the heart to the treatment area. To mitigate cardiac toxicity, various strategies, including jaw tracking and Volumetric Modulated Arc Therapy (VMAT), have been proposed. This study investigates the dosimetric impact of VMAT plans with and without jaw tracking on the left anterior descending artery (LAD) dose and heart mean dose in post-mastectomy breast cancer patients. Ten patients previously treated with VMAT were evaluated, and the results …


Platelet-Derived Exerkine Cxcl4/Platelet Factor 4 Rejuvenates Hippocampal Neurogenesis And Restores Cognitive Function In Aged Mice, Odette Leiter, David Brici, Stephen J Fletcher, Xuan Ling Hilary Yong, Jocelyn Widagdo, Nicholas Matigian, Adam B Schroer, Gregor Bieri, Daniel G Blackmore, Perry F Bartlett, Victor Anggono, Saul A Villeda, Tara L Walker Aug 2023

Platelet-Derived Exerkine Cxcl4/Platelet Factor 4 Rejuvenates Hippocampal Neurogenesis And Restores Cognitive Function In Aged Mice, Odette Leiter, David Brici, Stephen J Fletcher, Xuan Ling Hilary Yong, Jocelyn Widagdo, Nicholas Matigian, Adam B Schroer, Gregor Bieri, Daniel G Blackmore, Perry F Bartlett, Victor Anggono, Saul A Villeda, Tara L Walker

Faculty, Staff and Student Publications

The beneficial effects of physical activity on brain ageing are well recognised, with exerkines, factors that are secreted into the circulation in response to exercise, emerging as likely mediators of this response. However, the source and identity of these exerkines remain unclear. Here we provide evidence that an anti-geronic exerkine is secreted by platelets. We show that platelets are activated by exercise and are required for the exercise-induced increase in hippocampal precursor cell proliferation in aged mice. We also demonstrate that increasing the systemic levels of the platelet-derived exerkine CXCL4/platelet factor 4 (PF4) ameliorates age-related regenerative and cognitive impairments in …


Dynamics Of Anti-Influenza Mucosal Iga Over A Season In A Cohort Of Individuals Living Or Working In A Long-Term Care Facility, Matt D T Hitchings, Brooke A Borgert, Adam Shir, Bingyi Yang, Kyra H Grantz, Jacob Ball, Carlos A Moreno, Kenneth Rand, Parker A Small, Keith R Fowke, Derek A T Cummings Aug 2023

Dynamics Of Anti-Influenza Mucosal Iga Over A Season In A Cohort Of Individuals Living Or Working In A Long-Term Care Facility, Matt D T Hitchings, Brooke A Borgert, Adam Shir, Bingyi Yang, Kyra H Grantz, Jacob Ball, Carlos A Moreno, Kenneth Rand, Parker A Small, Keith R Fowke, Derek A T Cummings

Faculty, Staff and Student Publications

BACKGROUND: Serological surveys are used to ascertain influenza infection and immunity, but evidence for the utility of mucosal immunoglobulin A (IgA) as a correlate of infection or protection is limited.

METHODS: We performed influenza-like illness (ILI) surveillance on 220 individuals living or working in a retirement community in Gainesville, Florida from January to May 2018, and took pre- and postseason nasal samples of 11 individuals with polymerase chain reaction (PCR)-confirmed influenza infection and 60 randomly selected controls. Mucosal IgA against 10 strains of influenza was measured from nasal samples.

RESULTS: Overall, 28.2% and 11.3% of individuals experienced a 2-fold and …


Liposome-Based Carriers For Crispr Genome Editing, Xing Yin, Romain Harmancey, David D Mcpherson, Hyunggun Kim, Shao-Ling Huang Aug 2023

Liposome-Based Carriers For Crispr Genome Editing, Xing Yin, Romain Harmancey, David D Mcpherson, Hyunggun Kim, Shao-Ling Huang

Faculty, Staff and Student Publications

The CRISPR-based genome editing technology, known as clustered regularly interspaced short palindromic repeats (CRISPR), has sparked renewed interest in gene therapy. This interest is accompanied by the development of single-guide RNAs (sgRNAs), which enable the introduction of desired genetic modifications at the targeted site when used alongside the CRISPR components. However, the efficient delivery of CRISPR/Cas remains a challenge. Successful gene editing relies on the development of a delivery strategy that can effectively deliver the CRISPR cargo to the target site. To overcome this obstacle, researchers have extensively explored non-viral, viral, and physical methods for targeted delivery of CRISPR/Cas9 and …


Automated Lung Ultrasound Pulmonary Disease Quantification Using An Unsupervised Machine Learning Technique For Covid-19, Hersh Sagreiya, Michael A Jacobs, Alireza Akhbardeh Aug 2023

Automated Lung Ultrasound Pulmonary Disease Quantification Using An Unsupervised Machine Learning Technique For Covid-19, Hersh Sagreiya, Michael A Jacobs, Alireza Akhbardeh

Faculty, Staff and Student Publications

COVID-19 is an ongoing global health pandemic. Although COVID-19 can be diagnosed with various tests such as PCR, these tests do not establish pulmonary disease burden. Whereas point-of-care lung ultrasound (POCUS) can directly assess the severity of characteristic pulmonary findings of COVID-19, the advantage of using US is that it is inexpensive, portable, and widely available for use in many clinical settings. For automated assessment of pulmonary findings, we have developed an unsupervised learning technique termed the calculated lung ultrasound (CLU) index. The CLU can quantify various types of lung findings, such as A or B lines, consolidations, and pleural …


Surgical Delay Of Thoracodorsal Artery Perforator Flaps For Bilateral Autologous Breast Reconstruction, Ryan D. Hoffman, Mark A. Maier, Hugo St. Hilaire, Robert J. Allen Aug 2023

Surgical Delay Of Thoracodorsal Artery Perforator Flaps For Bilateral Autologous Breast Reconstruction, Ryan D. Hoffman, Mark A. Maier, Hugo St. Hilaire, Robert J. Allen

School of Medicine Faculty Publications

Summary; Autologous reconstruction accounts for nearly one-quarter of all breast reconstruction cases in the United States, with the abdomen functioning as the most popular donor site. This case describes a 62-year-old woman who presented to our clinic with a remote history of estrogen receptor+/progesterone+ breast cancer and bilateral implant-based reconstruction. After grade IV capsular contracture of her left breast, she presented for autologous reconstruction. Due to her body habitus and prior belt lipectomy, deep inferior epigastric perforator flap reconstruction was contra-indicated. The thoracodorsal artery perforator (TDAP) flap is well described in the literature, and was chosen as an alternative salvage …


Genome-Wide Association Studies And Fine-Mapping Identify Genomic Loci For N-3 And N-6 Polyunsaturated Fatty Acids In Hispanic American And African American Cohorts, Chaojie Yang, Jenna Veenstra, Traci M Bartz, Matthew C Pahl, Brian Hallmark, Yii-Der Ida Chen, Jason Westra, Lyn M Steffen, Christopher D Brown, David Siscovick, Michael Y Tsai, Alexis C Wood, Stephen S Rich, Caren E Smith, Timothy D O'Connor, Dariush Mozaffarian, Struan F A Grant, Floyd H Chilton, Nathan L Tintle, Rozenn N Lemaitre, Ani Manichaikul Aug 2023

Genome-Wide Association Studies And Fine-Mapping Identify Genomic Loci For N-3 And N-6 Polyunsaturated Fatty Acids In Hispanic American And African American Cohorts, Chaojie Yang, Jenna Veenstra, Traci M Bartz, Matthew C Pahl, Brian Hallmark, Yii-Der Ida Chen, Jason Westra, Lyn M Steffen, Christopher D Brown, David Siscovick, Michael Y Tsai, Alexis C Wood, Stephen S Rich, Caren E Smith, Timothy D O'Connor, Dariush Mozaffarian, Struan F A Grant, Floyd H Chilton, Nathan L Tintle, Rozenn N Lemaitre, Ani Manichaikul

Faculty, Staff and Students Publications

Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) play critical roles in human health. Prior genome-wide association studies (GWAS) of n-3 and n-6 PUFAs in European Americans from the CHARGE Consortium have documented strong genetic signals in/near the FADS locus on chromosome 11. We performed a GWAS of four n-3 and four n-6 PUFAs in Hispanic American (n = 1454) and African American (n = 2278) participants from three CHARGE cohorts. Applying a genome-wide significance threshold of P < 5 × 10


Combining Native Mass Spectrometry And Lipidomics To Uncover Specific Membrane Protein-Lipid Interactions From Natural Lipid Sources, Yun Zhu, Melanie T Odenkirk, Pei Qiao, Tianqi Zhang, Samantha Schrecke, Ming Zhou, Michael T Marty, Erin S Baker, Arthur Laganowsky Aug 2023

Combining Native Mass Spectrometry And Lipidomics To Uncover Specific Membrane Protein-Lipid Interactions From Natural Lipid Sources, Yun Zhu, Melanie T Odenkirk, Pei Qiao, Tianqi Zhang, Samantha Schrecke, Ming Zhou, Michael T Marty, Erin S Baker, Arthur Laganowsky

Faculty, Staff and Students Publications

While it is known that lipids play an essential role in regulating membrane protein structure and function, it remains challenging to identify specific protein-lipid interactions. Here, we present an innovative approach that combines native mass spectrometry (MS) and lipidomics to identify lipids retained by membrane proteins from natural lipid extracts. Our results reveal that the bacterial ammonia channel (AmtB) enriches specific cardiolipin (CDL) and phosphatidylethanolamine (PE) from natural headgroup extracts. When the two extracts are mixed, AmtB retains more species, wherein selectivity is tuned to bias headgroup selection. Using a series of natural headgroup extracts, we show TRAAK, a two-pore …


Class-Driven Synergy And Antagonism Between A Pseudomonas Phage And Antibiotics, Paul Nicholls, Justin R Clark, Carmen Gu Liu, Austen Terwilliger, Anthony W Maresso Aug 2023

Class-Driven Synergy And Antagonism Between A Pseudomonas Phage And Antibiotics, Paul Nicholls, Justin R Clark, Carmen Gu Liu, Austen Terwilliger, Anthony W Maresso

Faculty, Staff and Students Publications

The ubiquitous bacterial pathogen Pseudomonas aeruginosa is responsible for severe infections in patients with burns, cystic fibrosis, and neutropenia. Biofilm formation gives physical refuge and a protected microenvironment for sessile cells, rendering cure by antibiotics a challenge. Bacteriophages have evolved to prey on these biofilms over millions of years, using hydrolases and depolymerases to penetrate biofilms and reach cellular targets. Here, we assessed how a newly discovered KMV-like phage (ΦJB10) interacts with antibiotics to treat P. aeruginosa more effectively in both planktonic and biofilm forms. By testing representatives of four classes of antibiotics (cephalosporins, aminoglycosides, fluoroquinolones, and carbapenems), we demonstrated …


A Comparison Of Bleeding Risk In Patients With Cardiovascular Disease Treated With Aspirin Versus Clopidogrel, Laboy Alyssa Aug 2023

A Comparison Of Bleeding Risk In Patients With Cardiovascular Disease Treated With Aspirin Versus Clopidogrel, Laboy Alyssa

Master of Science in Physician Assistant Studies Capstone Presentations (Center City)

Background

Cardiovascular disease is the leading cause of death for men and women in the United States.7­­

There are four main types of CVD:

  1. Coronary heart disease
  2. Strokes & TIAs
  3. Peripheral arterial disease
  4. Aortic disease

Coronary artery disease (CAD) is the most prevalent and most common cause of atherosclerosis

Antiplatelet medications remain the cornerstone of medical therapy for primary and secondary atherosclerotic CAD prevention.

Aspirin is prescribed for:

  • Individuals with a history of MI or ischemic stroke to prevent a recurrence.
  • When a myocardial infarction (MI) is suspected to avoid further infarction.
  • Thromboembolism prevention after hip surgeries, transient …


The Impact Of Police Transport Of Patients With Penetrating Traumas On Mortality, Breanne Grove Aug 2023

The Impact Of Police Transport Of Patients With Penetrating Traumas On Mortality, Breanne Grove

Master of Science in Physician Assistant Studies Capstone Presentations (Center City)

Introduction

  • 2020: For people aged 1 to 44 in the U.S., firearm-related injuries ranked in the top five leading causes of death.1
  • 2022: 44,343 total gun violence deaths, 38,593 gun injuries & 646 mass shootings2
  • 1987: Philadelphia became first U.S. municipality to allow police personnel to follow a “scoop and run” policy.3,4 Necessity for police transport came from the lack of EMS availability when firearm homicide rates rose by 123%.5


Mobile Health As A Potential Tool To Treat Children In Obesity, Olivia Carey Aug 2023

Mobile Health As A Potential Tool To Treat Children In Obesity, Olivia Carey

Master of Science in Physician Assistant Studies Capstone Presentations (Center City)

Introduction

  • Pediatric obesity prevalence is estimated to be 22% in 2020 of all children in the US3
  • Obesity is defined as greater or equal to the 95th percentile for age and sex4
  • Childhood obesity leads to adulthood hypertension, hyperlipidemia, respiratory complications, and reduced quality of life44
  • The AAP released new 2023 guidelines that define the standard of care as a multi-modal, chronic-care treatment plan that prescribes healthy eating choices, an increase in physical activity, and mental health support.5
  • Mobile health is the use of mobile phones and wireless technology in healthcare3
  • A meta analysis of …


Trauma-Informed Care Pa-S Pilot Program Evaluation, Karyn Furcolo, Raya Patel, Mihail Petrov, Leslie Rowland Aug 2023

Trauma-Informed Care Pa-S Pilot Program Evaluation, Karyn Furcolo, Raya Patel, Mihail Petrov, Leslie Rowland

Master of Science in Physician Assistant Studies Capstone Presentations (Center City)

Background

Trauma stimulates the sympathetic nervous system, creates a fight-or-flight response through the hypothalamic-pituitary-adrenal axis, release of cortisol.1 Repeated stress leads to dysregulation of this response, which can lead to altered stress susceptibility and the inability to cope with stress.2 A trauma-informed approach encourages the provision of care to be based on knowledge and understanding of trauma and its widespread implications on patients lives.3

- Rather than asking "what is wrong with you," trauma-informed care encourages providers to ask "what happened to you?"5


Brain Arteriovenous Malformations: The Long Way Ahead In Physics, Chemistry And Mr-Angiography Practice Before Fully Replacing Digital Subtraction Angiography., Subhendra N. Sarkar Aug 2023

Brain Arteriovenous Malformations: The Long Way Ahead In Physics, Chemistry And Mr-Angiography Practice Before Fully Replacing Digital Subtraction Angiography., Subhendra N. Sarkar

Publications and Research

Typically, only high field systems are equipped with stronger gradients and short RF pulse designs, a must for high temporal resolution that are also responsible for high SAR, high susceptibility as well as neurostimulation. Gradient induced image noise tends to be high at 3T. Often vendors try to ameliorate such increased image noise with multi-channel head arrays and aggressive filter designs allowing an appearance of high SNR and CNR quality; however, the achievable SNR and CNR in the AVM remain limited as the analyzed articles by Zhuo et al seem to have in common. A short term solution to harvest …


Pocus Use For Emergency Airway Management In Rural Emergency Departments, Margaret Downing Aug 2023

Pocus Use For Emergency Airway Management In Rural Emergency Departments, Margaret Downing

Master of Science in Physician Assistant Studies Capstone Presentations (Center City)

Introduction

- Preparation and accurate prediction of difficult airways in emergent situations is necessary for successful first pass intubation

- Current methods for airway assessments require patient cooperation and may vary by provider

  • Mallampati score: open mouth, protrude tongue, see what structures are visible3
  • LEMON criteria: look externally, evaluate 3-3-2 rule, Mallampati score, obstruction, neck mobility
  • Thyromental distance: measure thyroid cartilage to tip of chin with neck extended3

- Difficult airways have successful first pass intubation only 82.2% of the time (vs 92.4% for non-difficult airways)6

- Adverse effects occurred in 14.2% of patients with successful first …


In Stable Phase Copd Patients Does Oral Magnesium Supplementation Vs Nothing Decrease The Number Of Copd Related Hospitalizations?, Georgina Garvey Aug 2023

In Stable Phase Copd Patients Does Oral Magnesium Supplementation Vs Nothing Decrease The Number Of Copd Related Hospitalizations?, Georgina Garvey

Master of Science in Physician Assistant Studies Capstone Presentations (Center City)

Introduction

- Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disease that leads to significant morbidity and mortality. Magnesium deficiency is known to lead to increased risk of both respiratory and cardiovascular diseases1. This deficiency can lead to an inflammatory state and increased bronchoconstriction that would exacerbate a disease state like COPD.2 Magnesium deficiency is seen in aging populations and those with chronic diseases3 and has also been seen in the population of patients coming into the emergency room with acute exacerbations of COPD.4

- Treatment with IV magnesium has been shown to be efficacious in …


Tranexamic Use And Safety In Adult Trauma Patients, Drew Frankenfield Aug 2023

Tranexamic Use And Safety In Adult Trauma Patients, Drew Frankenfield

Master of Science in Physician Assistant Studies Capstone Presentations (Center City)

Problem

  • Trauma is one of the top leading causes of death worldwide with about 1.9 million deaths per year.
  • Mortality due to hemorrhaging trauma, specifically, accounts for 30-40% of all trauma deaths.8
  • Mortality is due in part to trauma-induced coagulopathy which has simultaneous bleeding and clotting


Small Molecules Targeting Insm1 For The Treatment Of High-Risk Neuroblastoma, Michael S. Lan, Chiachen Chen Aug 2023

Small Molecules Targeting Insm1 For The Treatment Of High-Risk Neuroblastoma, Michael S. Lan, Chiachen Chen

School of Medicine Faculty Publications

Human neuroblastoma (NB) is the most common childhood extracranial tumor arising from the sympathetic nervous system. It is also a clinically heterogeneous disease that ranges from spontaneous regression to high-risk stage 4 disease. The cause of this disease remains elusive. However, the amplification of NMYC oncogene occurred in roughly 30% of NB patients, which strongly correlated with the advanced stage of disease subtype and the worse prognosis status. We discovered that N-Myc oncoprotein binds and activates INSM1, a zinc-finger transcription factor of neuroendocrine tumors. We also found that INSM1 modulates N-Myc stability mediated through PI3K/AKT/GSK3β signaling pathway. Therefore, INSM1 emerges …


Anterior Shoulder Instability And Open Procedures: History, Indications, And Clinical Outcomes, Mohamad Y. Fares, Peter Boufadel, Mohammad Daher, Jonathan Koa, Akshay Khanna, Joseph A. Abboud Aug 2023

Anterior Shoulder Instability And Open Procedures: History, Indications, And Clinical Outcomes, Mohamad Y. Fares, Peter Boufadel, Mohammad Daher, Jonathan Koa, Akshay Khanna, Joseph A. Abboud

Rothman Institute Papers

The shoulder, being the most mobile joint in the human body, is often susceptible to dislocations and subluxations more so than other joints. As such, shoulder instability constitutes a common complaint among patients worldwide, especially those who are young, participate in contact sports, and have increased innate flexibility in their joints. Management options in the setting of instability vary between conservative and surgical options that aim to mitigate symptoms and allow return of function. Surgical options can be arthroscopic and open, with a general shift among surgeons towards utilizing arthroscopic surgery in the past several decades. Nevertheless, open procedures still …


Targeting Bcl2 Overcomes Resistance And Augments Response To Aurora Kinase B Inhibition By Azd2811 In Small Cell Lung Cancer, Kavya Ramkumar, Azusa Tanimoto, Carminia M Della Corte, C Allison Stewart, Qi Wang, Li Shen, Robert J Cardnell, Jing Wang, Urszula M Polanska, Courtney Andersen, Jamal Saeh, J Elizabeth Pease, Jon Travers, Giulia Fabbri, Carl M Gay, Jelena Urosevic, Lauren A Byers Aug 2023

Targeting Bcl2 Overcomes Resistance And Augments Response To Aurora Kinase B Inhibition By Azd2811 In Small Cell Lung Cancer, Kavya Ramkumar, Azusa Tanimoto, Carminia M Della Corte, C Allison Stewart, Qi Wang, Li Shen, Robert J Cardnell, Jing Wang, Urszula M Polanska, Courtney Andersen, Jamal Saeh, J Elizabeth Pease, Jon Travers, Giulia Fabbri, Carl M Gay, Jelena Urosevic, Lauren A Byers

Faculty, Staff and Student Publications

PURPOSE: Therapeutic resistance to frontline therapy develops rapidly in small cell lung cancer (SCLC). Treatment options are also limited by the lack of targetable driver mutations. Therefore, there is an unmet need for developing better therapeutic strategies and biomarkers of response. Aurora kinase B (AURKB) inhibition exploits an inherent genomic vulnerability in SCLC and is a promising therapeutic approach. Here, we identify biomarkers of response and develop rational combinations with AURKB inhibition to improve treatment efficacy.

EXPERIMENTAL DESIGN: Selective AURKB inhibitor AZD2811 was profiled in a large panel of SCLC cell lines (n = 57) and patient-derived xenograft (PDX) models. …


Enigma Chek2gether Project: A Comprehensive Study Identifies Functionally Impaired Chek2 Germline Missense Variants Associated With Increased Breast Cancer Risk, Lenka Stolarova, Petra Kleiblova, Petra Zemankova, Barbora Stastna, Marketa Janatova, Jana Soukupova, Maria Isabel Achatz, Christine Ambrosone, Paraskevi Apostolou, Banu K Arun, Paul Auer, Mollie Barnard, Birgitte Bertelsen, Biobank Japan, Marinus J Blok, Nicholas Boddicker, Joan Brunet, Elizabeth S Burnside, Mariarosaria Calvello, Ian Campbell, Sock Hoai Chan, Fei Chen, Jian Bang Chiang, Anna Coppa, Laura Cortesi, Ana Crujeiras-González, Consortium Czecanca, Kim De Leeneer, Robin De Putter, Allison Depersia, Lisa Devereux, Susan Domchek, Anna Efremidis, Christoph Engel, Corinna Ernst, D Gareth R Evans, Lidia Feliubadaló, Florentia Fostira, Olivia Fuentes-Ríos, Encarna B Gómez-García, Sara González, Christopher Haiman, Thomas Van Overeem Hansen, Jan Hauke, James Hodge, Chunling Hu, Hongyan Huang, Nur Diana Binte Ishak, Yusuke Iwasaki, Irene Konstantopoulou, Peter Kraft, James Lacey, Conxi Lázaro, Na Li, Weng Khong Lim, Sara Lindstrom, Adriana Lori, Elana Martinez, Alexandra Martins, Koichi Matsuda, Giuseppe Matullo, Simone Mcinerny, Kyriaki Michailidou, Marco Montagna, Alvaro N A Monteiro, Luigi Mori, Katherine Nathanson, Susan L Neuhausen, Heli Nevanlinna, Janet E Olson, Julie Palmer, Barbara Pasini, Alpa Patel, Maria Piane, Bruce Poppe, Paolo Radice, Alessandra Renieri, Nicoletta Resta, Marcy E Richardson, Toon Rosseel, Kathryn J Ruddy, Marta Santamariña, Elizabeth Santana Dos Santos, Lauren Teras, Amanda E Toland, Amy Trentham-Dietz, Celine M Vachon, Alexander E Volk, Nana Weber-Lassalle, Jeffrey N Weitzel, Lisa Wiesmuller, Stacey Winham, Siddhartha Yadav, Drakoulis Yannoukakos, Song Yao, Valentina Zampiga, Magnus Zethoven, Ze Wen Zhang, Tomas Zima, Amanda B Spurdle, Ana Vega, Maria Rossing, Jesús Del Valle, Arcangela De Nicolo, Eric Hahnen, Kathleen B M Claes, Joanne Ngeow, Yukihide Momozawa, Paul A James, Fergus J Couch, Libor Macurek, Zdenek Kleibl Aug 2023

Enigma Chek2gether Project: A Comprehensive Study Identifies Functionally Impaired Chek2 Germline Missense Variants Associated With Increased Breast Cancer Risk, Lenka Stolarova, Petra Kleiblova, Petra Zemankova, Barbora Stastna, Marketa Janatova, Jana Soukupova, Maria Isabel Achatz, Christine Ambrosone, Paraskevi Apostolou, Banu K Arun, Paul Auer, Mollie Barnard, Birgitte Bertelsen, Biobank Japan, Marinus J Blok, Nicholas Boddicker, Joan Brunet, Elizabeth S Burnside, Mariarosaria Calvello, Ian Campbell, Sock Hoai Chan, Fei Chen, Jian Bang Chiang, Anna Coppa, Laura Cortesi, Ana Crujeiras-González, Consortium Czecanca, Kim De Leeneer, Robin De Putter, Allison Depersia, Lisa Devereux, Susan Domchek, Anna Efremidis, Christoph Engel, Corinna Ernst, D Gareth R Evans, Lidia Feliubadaló, Florentia Fostira, Olivia Fuentes-Ríos, Encarna B Gómez-García, Sara González, Christopher Haiman, Thomas Van Overeem Hansen, Jan Hauke, James Hodge, Chunling Hu, Hongyan Huang, Nur Diana Binte Ishak, Yusuke Iwasaki, Irene Konstantopoulou, Peter Kraft, James Lacey, Conxi Lázaro, Na Li, Weng Khong Lim, Sara Lindstrom, Adriana Lori, Elana Martinez, Alexandra Martins, Koichi Matsuda, Giuseppe Matullo, Simone Mcinerny, Kyriaki Michailidou, Marco Montagna, Alvaro N A Monteiro, Luigi Mori, Katherine Nathanson, Susan L Neuhausen, Heli Nevanlinna, Janet E Olson, Julie Palmer, Barbara Pasini, Alpa Patel, Maria Piane, Bruce Poppe, Paolo Radice, Alessandra Renieri, Nicoletta Resta, Marcy E Richardson, Toon Rosseel, Kathryn J Ruddy, Marta Santamariña, Elizabeth Santana Dos Santos, Lauren Teras, Amanda E Toland, Amy Trentham-Dietz, Celine M Vachon, Alexander E Volk, Nana Weber-Lassalle, Jeffrey N Weitzel, Lisa Wiesmuller, Stacey Winham, Siddhartha Yadav, Drakoulis Yannoukakos, Song Yao, Valentina Zampiga, Magnus Zethoven, Ze Wen Zhang, Tomas Zima, Amanda B Spurdle, Ana Vega, Maria Rossing, Jesús Del Valle, Arcangela De Nicolo, Eric Hahnen, Kathleen B M Claes, Joanne Ngeow, Yukihide Momozawa, Paul A James, Fergus J Couch, Libor Macurek, Zdenek Kleibl

Faculty, Staff and Student Publications

PURPOSE: Germline pathogenic variants in CHEK2 confer moderately elevated breast cancer risk (odds ratio, OR ∼ 2.5), qualifying carriers for enhanced breast cancer screening. Besides pathogenic variants, dozens of missense CHEK2 variants of uncertain significance (VUS) have been identified, hampering the clinical utility of germline genetic testing (GGT).

EXPERIMENTAL DESIGN: We collected 460 CHEK2 missense VUS identified by the ENIGMA consortium in 15 countries. Their functional characterization was performed using CHEK2-complementation assays quantifying KAP1 phosphorylation and CHK2 autophosphorylation in human RPE1-CHEK2-knockout cells. Concordant results in both functional assays were used to categorize CHEK2 VUS from 12 ENIGMA case-control datasets, including …


Estrogen-Related Receptor Gamma Gene Therapy Promotes Therapeutic Angiogenesis And Muscle Recovery In Preclinical Model Of Pad, Danesh H Sopariwala, Andrea S Rios, Addison Saley, Ashok Kumar, Vihang A Narkar Aug 2023

Estrogen-Related Receptor Gamma Gene Therapy Promotes Therapeutic Angiogenesis And Muscle Recovery In Preclinical Model Of Pad, Danesh H Sopariwala, Andrea S Rios, Addison Saley, Ashok Kumar, Vihang A Narkar

Faculty, Staff and Student Publications

Background Peripheral arterial disease and critical limb ischemia are cardiovascular complications associated with vascular insufficiency, oxidative metabolic dysfunction, and myopathy in the limbs. Estrogen-related receptor gamma (ERRγ) has emerged as a dual regulator of paracrine angiogenesis and oxidative metabolism through transgenic mouse studies. Here our objective was to investigate whether postischemic intramuscular targeting of ERRγ via gene therapy promotes ischemic recovery in a preclinical model of peripheral arterial disease/critical limb ischemia. Methods and Results Adeno-associated virus 9 (AAV9)


Protein-Energy Malnutrition Is Associated With Worse Outcomes In Patients With Atrial Fibrillation: A Nationwide Analysis, Favour Markson, Emmanuel Akuna, Iriagbonse Asemota, Gabriel Areoye, Anoz Shahi, Praise Nwachukwu, Kenneth Ong Aug 2023

Protein-Energy Malnutrition Is Associated With Worse Outcomes In Patients With Atrial Fibrillation: A Nationwide Analysis, Favour Markson, Emmanuel Akuna, Iriagbonse Asemota, Gabriel Areoye, Anoz Shahi, Praise Nwachukwu, Kenneth Ong

Einstein Health Papers

Protein–energy malnutrition (PEM), which leads to a reduced ability of tissues to regenerate and repair themselves, may exacerbate many chronic diseases, including atrial fibrillation (AF), which occurs as a response of the heart to chronic inflammation. However, population-based studies examining the association between PEM and the prevalence and health care burden of AF are lacking. The aim of this retrospective cohort study was to estimate the impact of PEM on the prevalence and clinical outcomes of hospitalization for AF. The National Inpatient Sample (NIS) 2016 and 2017 datasets were searched for data on hospitalized adult patients with AF as a …


Home-Based Self-Sampling Vs Clinician Sampling For Anal Precancer Screening: The Prevent Anal Cancer Self-Swab Study, Alan G Nyitray, Jenna Nitkowski, Timothy L Mcauliffe, Bridgett Brzezinski, Michael D Swartz, María E Fernandez, Ashish A Deshmukh, Timothy J Ridolfi, Sarah J Lundeen, Leslie Cockerham, Dave Wenten, Andrew Petroll, Brian Hilgeman, Jennifer S Smith, Elizabeth Y Chiao, Anna R Giuliano, Vanessa Schick, Prevent Anal Cancer Self-Swab Study Team Aug 2023

Home-Based Self-Sampling Vs Clinician Sampling For Anal Precancer Screening: The Prevent Anal Cancer Self-Swab Study, Alan G Nyitray, Jenna Nitkowski, Timothy L Mcauliffe, Bridgett Brzezinski, Michael D Swartz, María E Fernandez, Ashish A Deshmukh, Timothy J Ridolfi, Sarah J Lundeen, Leslie Cockerham, Dave Wenten, Andrew Petroll, Brian Hilgeman, Jennifer S Smith, Elizabeth Y Chiao, Anna R Giuliano, Vanessa Schick, Prevent Anal Cancer Self-Swab Study Team

Faculty, Staff and Student Publications

Sexual minority men are at increased risk for anal squamous cell carcinoma. Our objective was to compare screening engagement among individuals randomized to self-collect an anal canal specimen at home or to attend a clinic appointment. Specimen adequacy was then assessed for human papillomavirus (HPV) DNA genotyping. A randomized trial recruited cisgendered sexual minority men and transgender people in the community and assigned them to use a home-based self-collection swabbing kit or attend a clinic-based swabbing. Swabs were sent for HPV genotyping. The proportions of participants completing screening in each study arm and the adequacy of their specimens for HPV …


Pelvic Fractures - An Overview, Shashank Cheemalapati Aug 2023

Pelvic Fractures - An Overview, Shashank Cheemalapati

Digital Journal of Clinical Medicine

Pelvic fractures are injuries commonly caused by high-energy trauma, such as motor vehicle accidents and falls from a height. Understanding the anatomy, mechanisms of injury, classification, diagnosis and the management of these fractures is crucial to improve patient outcomes. This short article aims to provide a comprehensive overview of the current state of knowledge regarding pelvic fractures.


A Multidimensional Connectomics- And Radiomics-Based Advanced Machine-Learning Framework To Distinguish Radiation Necrosis From True Progression In Brain Metastases, Yilin Cao, Vishwa S Parekh, Emerson Lee, Xuguang Chen, Kristin J Redmond, Jay J Pillai, Luke Peng, Michael A Jacobs, Lawrence R Kleinberg Aug 2023

A Multidimensional Connectomics- And Radiomics-Based Advanced Machine-Learning Framework To Distinguish Radiation Necrosis From True Progression In Brain Metastases, Yilin Cao, Vishwa S Parekh, Emerson Lee, Xuguang Chen, Kristin J Redmond, Jay J Pillai, Luke Peng, Michael A Jacobs, Lawrence R Kleinberg

Faculty, Staff and Student Publications

We introduce tumor connectomics, a novel MRI-based complex graph theory framework that describes the intricate network of relationships within the tumor and surrounding tissue, and combine this with multiparametric radiomics (mpRad) in a machine-learning approach to distinguish radiation necrosis (RN) from true progression (TP). Pathologically confirmed cases of RN vs. TP in brain metastases treated with SRS were included from a single institution. The region of interest was manually segmented as the single largest diameter of the T1 post-contrast (T1C) lesion plus the corresponding area of T2 FLAIR hyperintensity. There were 40 mpRad features and 6 connectomics features extracted, as …


Spatial Immunoprofiling Of Adenoid Cystic Carcinoma Reveals B7-H4 Is A Therapeutic Target For Aggressive Tumors, Luana Guimaraes Sousa, Daniel J Mcgrail, Felippe Lazar Neto, Kaiyi Li, Mario L Marques-Piubelli, Sammy Ferri-Borgogno, Hui Dai, Yoshitsugu Mitani, Nicole Spardy Burr, Zachary A Cooper, Krista Kinneer, Maria Angelica Cortez, Shiaw-Yih Lin, Diana Bell, Adel El Naggar, Jared Burks, Renata Ferrarotto Aug 2023

Spatial Immunoprofiling Of Adenoid Cystic Carcinoma Reveals B7-H4 Is A Therapeutic Target For Aggressive Tumors, Luana Guimaraes Sousa, Daniel J Mcgrail, Felippe Lazar Neto, Kaiyi Li, Mario L Marques-Piubelli, Sammy Ferri-Borgogno, Hui Dai, Yoshitsugu Mitani, Nicole Spardy Burr, Zachary A Cooper, Krista Kinneer, Maria Angelica Cortez, Shiaw-Yih Lin, Diana Bell, Adel El Naggar, Jared Burks, Renata Ferrarotto

Faculty, Staff and Student Publications

PURPOSE: Adenoid cystic carcinoma (ACC) is a heterogeneous malignancy, and no effective systemic therapy exists for metastatic disease. We previously described two prognostic ACC molecular subtypes with distinct therapeutic vulnerabilities, ACC-I and ACC-II. In this study, we explored the ACC tumor microenvironment (TME) using RNA-sequencing and spatial biology to identify potential therapeutic targets.

EXPERIMENTAL DESIGN: Tumor samples from 62 ACC patients with available RNA-sequencing data that had been collected as part of previous studies were stained with a panel of 28 validated metal-tagged antibodies. Imaging mass cytometry (IMC) was performed using the Fluidigm Helios CyTOF instrument and analyzed with Visiopharm …