Medical Specialties Commons^™

The Impact Of Changes In Depression On Cardiovascular Outcomes In Patients With Coronary Heart Disease., Nishant Vatsa, Josiah Bennett, Sonika Vatsa, Alireza Rahbar, Daniel A Gold, Vardhmaan Jain, Matthew E Gold, Alexander Razavi, Adithya Yadalam, Shivang Desai, Muhammad Owais, Joy D Hartsfield, Yi-An Ko, Laurence Sperling, Viola Vaccarino, Puja K Mehta, Arshed A Quyyumi

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Depression is associated with major adverse cardiovascular events (MACE). Whether longitudinal changes in depression affect MACE in patients with coronary heart disease (CHD) remains unknown.

OBJECTIVES: The authors evaluated the hypothesis that increasing or persistent depression predicts MACE in patients with CHD.

METHODS: At baseline, 3,483 Emory Cardiovascular Biobank participants (median age 65.5 years, 31.6% female) completed the Patient Health Questionnaire 8 (PHQ8) for depression evaluation. At 1 year, 2,639 of these event-free participants repeated the questionnaire. Depression was defined as a PHQ8 score >9 and change in depressive symptoms (Δ" role="presentation"> PHQ8) was year 1 score minus baseline …

Longitudinal Assessment Of Retinopathy Of Prematurity (Longrop) Study: Impacts Of Viewing Time And Ability To Compare On Detection Of Change, Tatiana R. Rosenblatt, Hashem H. Ghoraba, Marco H. Ji, Caroline R. Baumal, Audina M. Berrocal, Cagri G. Besirli, Kimberly A. Drenser, Anna L. Ells, C. Armitage Harper, G. Baker Hubbard, Eric D. Nudleman, Polly A. Quiram, Irena Tsui, Yoshihiro Yonekawa, Edward H. Wood, Jochen Kumm, Darius M. Moshfeghi

Wills Eye Hospital Papers

PURPOSE: This study compared two imaging grading techniques to assess the utility of longitudinal image-based analysis in retinopathy of prematurity (ROP) screening: (1) time-limited without image comparison (a proxy for bedside indirect ophthalmoscopy, termed sBIO) and time-unlimited with image comparison (for telemedicine grading, termed TELE) screening. We tested two hypotheses: (1) H1: TELE was superior to sBIO for the detection of change (Tempo)-same, better, or worse and (2) H2: granular data of change (e.g., at the image and feature level) is integrated by graders to achieve the Tempo assessment.

DESIGN: Prospective reliability analysis.

METHODS: Gold standard reference (GS) was a …

Tick-Borne Diseases And Pregnancy: A Narrative Review Evaluating Pregnancy Complications Caused By Tick-Borne Diseases, Michael W Curtis, Job E Lopez

Faculty, Staff and Students Publications

Ticks are vectors of public health concern because the pathogens they transmit can cause detrimental diseases in humans. Lyme disease, tick-borne relapsing fever, human granulocytic anaplasmosis, Rocky Mountain spotted fever, tick-borne encephalitis, Crimean-Congo hemorrhagic fever, and babesiosis are some of the most common diseases caused by the pathogens transmitted by ticks. The overlap between human activities and tick habitats is growing, contributing to an increase in tick-borne disease cases. Unfortunately, pregnancy as a risk factor for tick-borne diseases is largely ignored. In this narrative review we use case reports, epidemiological studies, and animal studies to evaluate the maternal, pregnancy, and …

Neurodevelopmental Disorder Caused By Deletion Of Chaserr, A Lncrna Gene, Vijay S Ganesh, Kevin Riquin, Nicolas Chatron, Esther Yoon, Kay-Marie Lamar, Miriam C Aziz, Pauline Monin, Melanie C O'Leary, Julia K Goodrich, Kiran V Garimella, Eleina England, Ben Weisburd, François Aguet, Carlos A Bacino, David R Murdock, Hongzheng Dai, Jill A Rosenfeld, Lisa T Emrick, Shamika Ketkar, Yael Sarusi, Damien Sanlaville, Saima Kayani, Brian Broadbent, Alisée Pengam, Bertrand Isidor, Stéphane Bezieau, Benjamin Cogné, Daniel G Macarthur, Igor Ulitsky, Gemma L Carvill, Anne O'Donnell-Luria

Faculty, Staff and Students Publications

No abstract provided.

Salvage Reirradiation With Proton Beam Therapy For Locoregionally Recurrent Non-Small Cell Lung Cancer, Matthew S Ning, Abigael Odwuor, Joe Y Chang, Saumil Gandhi, Zhongxing Liao, Steven H Lin, Aileen Chen, James W Welsh, Quynh-Nhu Nguyen, Michael S O'Reilly, Stephen G Chun, Julianna Bronk, David Qian, Percy Lee

Faculty, Staff and Student Publications

Background/objectives: This retrospective study evaluates outcomes of 66 patients who underwent reirradiation (re-RT) with proton beam therapy (PBT) for recurrent non-small cell lung cancer.

Methods: Toxicity was scored via the CTCAE v5.0, and outcomes estimated using the Kaplan-Meier method, with associations evaluated via Cox proportional hazards and logistic regression analyses.

Results: Patients were treated to a median re-RT prescription of 66 Gy/33 fxs (BED10 = 79 Gy; IQR: 71-84 Gy) at an interval of 1.4 years from prior RT. Half (50%) received concurrent chemotherapy. At 14 months follow-up, the median OS and PFS were 5 months (95%CI: 13-17) and 12.5 …

Aromatase, Testosterone, Tmprss2: Determinants Of Covid-19 Severity, Eric C Mohan, Jude P J Savarraj, Gabriela D Colpo, Diego Morales, Carson E Finger, Alexis Mcalister, Hilda Ahnstedt, Huimahn Choi, Louise D Mccullough, Bharti Manwani

Faculty, Staff and Student Publications

Background: Male sex has been identified as a risk factor for worse COVID-19 outcomes. This sex difference has been mostly attributed to the complex role of sex hormones. Cell surface entry of SARS-CoV-2 is mediated by the transmembrane protease serine 2 (TMPRSS2) which is under transcriptional regulation by androgens. P450 aromatase enzyme converts androgens to estrogens. This study measured concentrations of aromatase enzyme, testosterone, estradiol, and TMPRSS-2 in plasma of hospitalized COVID-19 patients to elucidate the dynamics of sex-linked disparity in COVID-19 and correlate them with disease severity and mortality.

Methods: In this prospective cohort study, a total of 265 …

Interpreting The Biological Effects Of Protons As A Function Of Physical Quantity: Linear Energy Transfer Or Microdosimetric Lineal Energy Spectrum?, Fada Guan, Lawrence Bronk, Matthew Kerr, Yuting Li, Leslie A Braby, Mary Sobieski, Xiaochun Wang, Xiaodong Zhang, Clifford Stephan, David R Grosshans, Radhe Mohan

Faculty, Staff and Student Publications

The choice of appropriate physical quantities to characterize the biological effects of ionizing radiation has evolved over time coupled with advances in scientific understanding. The basic hypothesis in radiation dosimetry is that the energy deposited by ionizing radiation initiates all the consequences of exposure in a biological sample (e.g., DNA damage, reproductive cell death). Physical quantities defined to characterize energy deposition have included dose, a measure of the mean energy imparted per unit mass of the target, and linear energy transfer (LET), a measure of the mean energy deposition per unit distance that charged particles traverse in a medium. The …

Childhood Neglect Is Associated With Alterations In Neural Prediction Error Signaling And The Response To Novelty, Joseph Aloi, Kathleen I Crum, Karina S Blair, Ru Zhang, Johannah Bashford-Largo, Sahil Bajaj, Soonjo Hwang, Bruno B Averbeck, Nim Tottenham, Matthew Dobbertin, R James R Blair

Faculty, Staff and Student Publications

Background: One in eight children experience early life stress (ELS), which increases risk for psychopathology. ELS, particularly neglect, has been associated with reduced responsivity to reward. However, little work has investigated the computational specifics of this disrupted reward response - particularly with respect to the neural response to Reward Prediction Errors (RPE) - a critical signal for successful instrumental learning - and the extent to which they are augmented to novel stimuli. The goal of the current study was to investigate the associations of abuse and neglect, and neural representation of RPE to novel and non-novel stimuli.

Methods: One hundred …

Interpreting The Biological Effects Of Protons As A Function Of Physical Quantity: Linear Energy Transfer Or Microdosimetric Lineal Energy Spectrum?, Fada Guan, Lawrence Bronk, Matthew Kerr, Yuting Li, Leslie A Braby, Mary Sobieski, Xiaochun Wang, Xiaodong Zhang, Clifford Stephan, David R Grosshans, Radhe Mohan

Faculty, Staff and Student Publications

The choice of appropriate physical quantities to characterize the biological effects of ionizing radiation has evolved over time coupled with advances in scientific understanding. The basic hypothesis in radiation dosimetry is that the energy deposited by ionizing radiation initiates all the consequences of exposure in a biological sample (e.g., DNA damage, reproductive cell death). Physical quantities defined to characterize energy deposition have included dose, a measure of the mean energy imparted per unit mass of the target, and linear energy transfer (LET), a measure of the mean energy deposition per unit distance that charged particles traverse in a medium. The …

Interpreting The Biological Effects Of Protons As A Function Of Physical Quantity: Linear Energy Transfer Or Microdosimetric Lineal Energy Spectrum?, Fada Guan, Lawrence Bronk, Matthew Kerr, Yuting Li, Leslie A Braby, Mary Sobieski, Xiaochun Wang, Xiaodong Zhang, Clifford Stephan, David R Grosshans, Radhe Mohan

Faculty, Staff and Student Publications

The choice of appropriate physical quantities to characterize the biological effects of ionizing radiation has evolved over time coupled with advances in scientific understanding. The basic hypothesis in radiation dosimetry is that the energy deposited by ionizing radiation initiates all the consequences of exposure in a biological sample (e.g., DNA damage, reproductive cell death). Physical quantities defined to characterize energy deposition have included dose, a measure of the mean energy imparted per unit mass of the target, and linear energy transfer (LET), a measure of the mean energy deposition per unit distance that charged particles traverse in a medium. The …

Interpreting The Biological Effects Of Protons As A Function Of Physical Quantity: Linear Energy Transfer Or Microdosimetric Lineal Energy Spectrum?, Fada Guan, Lawrence Bronk, Matthew Kerr, Yuting Li, Leslie A Braby, Mary Sobieski, Xiaochun Wang, Xiaodong Zhang, Clifford Stephan, David R Grosshans, Radhe Mohan

Faculty, Staff and Student Publications

The choice of appropriate physical quantities to characterize the biological effects of ionizing radiation has evolved over time coupled with advances in scientific understanding. The basic hypothesis in radiation dosimetry is that the energy deposited by ionizing radiation initiates all the consequences of exposure in a biological sample (e.g., DNA damage, reproductive cell death). Physical quantities defined to characterize energy deposition have included dose, a measure of the mean energy imparted per unit mass of the target, and linear energy transfer (LET), a measure of the mean energy deposition per unit distance that charged particles traverse in a medium. The …

Interpreting The Biological Effects Of Protons As A Function Of Physical Quantity: Linear Energy Transfer Or Microdosimetric Lineal Energy Spectrum?, Fada Guan, Lawrence Bronk, Matthew Kerr, Yuting Li, Leslie A Braby, Mary Sobieski, Xiaochun Wang, Xiaodong Zhang, Clifford Stephan, David R Grosshans, Radhe Mohan

Faculty, Staff and Student Publications

The choice of appropriate physical quantities to characterize the biological effects of ionizing radiation has evolved over time coupled with advances in scientific understanding. The basic hypothesis in radiation dosimetry is that the energy deposited by ionizing radiation initiates all the consequences of exposure in a biological sample (e.g., DNA damage, reproductive cell death). Physical quantities defined to characterize energy deposition have included dose, a measure of the mean energy imparted per unit mass of the target, and linear energy transfer (LET), a measure of the mean energy deposition per unit distance that charged particles traverse in a medium. The …

Interpreting The Biological Effects Of Protons As A Function Of Physical Quantity: Linear Energy Transfer Or Microdosimetric Lineal Energy Spectrum?, Fada Guan, Lawrence Bronk, Matthew Kerr, Yuting Li, Leslie A Braby, Mary Sobieski, Xiaochun Wang, Xiaodong Zhang, Clifford Stephan, David R Grosshans, Radhe Mohan

Faculty, Staff and Student Publications

The choice of appropriate physical quantities to characterize the biological effects of ionizing radiation has evolved over time coupled with advances in scientific understanding. The basic hypothesis in radiation dosimetry is that the energy deposited by ionizing radiation initiates all the consequences of exposure in a biological sample (e.g., DNA damage, reproductive cell death). Physical quantities defined to characterize energy deposition have included dose, a measure of the mean energy imparted per unit mass of the target, and linear energy transfer (LET), a measure of the mean energy deposition per unit distance that charged particles traverse in a medium. The …

Interpreting The Biological Effects Of Protons As A Function Of Physical Quantity: Linear Energy Transfer Or Microdosimetric Lineal Energy Spectrum?, Fada Guan, Lawrence Bronk, Matthew Kerr, Yuting Li, Leslie A Braby, Mary Sobieski, Xiaochun Wang, Xiaodong Zhang, Clifford Stephan, David R Grosshans, Radhe Mohan

Faculty, Staff and Student Publications

The choice of appropriate physical quantities to characterize the biological effects of ionizing radiation has evolved over time coupled with advances in scientific understanding. The basic hypothesis in radiation dosimetry is that the energy deposited by ionizing radiation initiates all the consequences of exposure in a biological sample (e.g., DNA damage, reproductive cell death). Physical quantities defined to characterize energy deposition have included dose, a measure of the mean energy imparted per unit mass of the target, and linear energy transfer (LET), a measure of the mean energy deposition per unit distance that charged particles traverse in a medium. The …

Pclaf-Dream Drives Alveolar Cell Plasticity For Lung Regeneration, Bongjun Kim, Yuanjian Huang, Kyung-Pil Ko, Shengzhe Zhang, Gengyi Zou, Jie Zhang, Moon Jong Kim, Danielle Little, Lisandra Vila Ellis, Margherita Paschini, Sohee Jun, Kwon-Sik Park, Jichao Chen, Carla Kim, Jae-Il Park

Faculty, Staff and Student Publications

Cell plasticity, changes in cell fate, is crucial for tissue regeneration. In the lung, failure of regeneration leads to diseases, including fibrosis. However, the mechanisms governing alveolar cell plasticity during lung repair remain elusive. We previously showed that PCLAF remodels the DREAM complex, shifting the balance from cell quiescence towards cell proliferation. Here, we find that PCLAF expression is specific to proliferating lung progenitor cells, along with the DREAM target genes transactivated by lung injury. Genetic ablation of Pclaf impairs AT1 cell repopulation from AT2 cells, leading to lung fibrosis. Mechanistically, the PCLAF-DREAM complex transactivates CLIC4, triggering TGF-β signaling activation, …

Identification Of Allele-Specific Kiv-2 Repeats And Impact On Lp(A) Measurements For Cardiovascular Disease Risk, Sairam Behera, Jonathan R Belyeu, Xiao Chen, Luis F Paulin, Ngoc Quynh H Nguyen, Emma Newman, Medhat Mahmoud, Vipin K Menon, Qibin Qi, Parag Joshi, Santica Marcovina, Massimiliano Rossi, Eric Roller, James Han, Vitor Onuchic, Christy L Avery, Christie M Ballantyne, Carlos J Rodriguez, Robert C Kaplan, Donna M Muzny, Ginger A Metcalf, Richard A Gibbs, Bing Yu, Eric Boerwinkle, Michael A Eberle, Fritz J Sedlazeck

Faculty, Staff and Students Publications

The abundance of Lp(a) protein holds significant implications for the risk of cardiovascular disease (CVD), which is directly impacted by the copy number (CN) of KIV-2, a 5.5 kbp sub-region. KIV-2 is highly polymorphic in the population and accurate analysis is challenging. In this study, we present the DRAGEN KIV-2 CN caller, which utilizes short reads. Data across 166 WGS show that the caller has high accuracy, compared to optical mapping and can further phase approximately 50% of the samples. We compared KIV-2 CN numbers to 24 previously postulated KIV-2 relevant SNVs, revealing that many are ineffective predictors of KIV-2 …

Observers Have Similar Improvements In Student Learning Outcomes As Participants In Athletic Training Simulation Education: A Pilot Study., Alma R. Mattocks Phd, Atc, Chse, Sara E. Mahoney Phd, Facsm, Rachele E. Vogelpohl Phd, Atc, Kim Hawkins Phd, Aprn, Fnp-C

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

Introduction: The use of standardized patient (SP) encounters in athletic training education programs have become more common; however, due to time and space constraints, it is possible that not all athletic training students will be able to participate and some must be observers. The objective of this study was to determine if observers experience similar improvements in student learning outcomes as participants for SP encounters. Methods: A pretest/posttest, non-randomized controlled trial was utilized. Nine athletic training students volunteered to participate in the research study. All participants completed a pretest survey including a knowledge assessment and confidence rating scale, followed by …

Relationship Between Posterior Tibial Artery Blood Flow And Lower Leg Flexibility Among Collegiate Runners, Jeffrey Williams, Megan Battles, Rachel Bowden, Cameron Greene, Arbin Thapaliya, Justin Stanek

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

Purpose: Understanding relationships between blood flow and muscle inflexibility in the lower leg can support improved healthcare competency. Sports medicine practitioners might use the reference ranges and knowledge of relationships among these variables to support effective health screenings among their competitive runners. These variables have been linked in other areas of the body where inflexibility in the pectoralis minor and scalene muscles have been associated with diminished blood flow to the upper limb. No studies, however, have examined the relationship between vascular and mobility characteristics in the lower legs of runners. Therefore, the purpose of this study was to examine …

Bidirectional Nature Of Work Family Conflict: Family Interfering With Work Conflict Among Athletic Trainers In The Collegiate Setting, Stephanie M. Singe, Milana Adaspour, Alexandrya Cairns, William Pitney

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

Introduction: Work-family conflict is bidirectional, yet research has largely only investigated the extent to which work interferes with family conflict (WIFC) and not whether family interferes with work conflict (FIWC). Objective: Investigate FIWC among collegiate athletic trainers. Specifically, we were focused on relationships between gender, marital status, employment status of the athletic trainer’s spouse, and number of children. Methods: Data were collected via a cross-sectional, online survey (Qualtrics). Descriptive statistics were calculated for demographic information; Mann Whitney U analyses were utilized to discover differences between gender, marital status, employment status of spouse, and number of children.

Results: 984 (605 women, …

Athletic Trainer Emergency Management Skill Assessment Via Low Fidelity Simulation, Jaclyn B. Arduini, Jennifer L. Volberding

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

Introduction: Athletic training education requires the inclusion of emergency management (EM) best practices, however the Board of Certification (BOC) does not mandate any continuing education (CE) past Emergency Cardiac Care (ECC). With EM best practices continuing to change there is potential for a large knowledge gap to develop in practicing athletic trainers (ATs) who do not chose to engage in EM CE. The purpose of this study was to identify knowledge gaps in practicing ATs’ EM skills via low fidelity simulation. Methods: A cross-sectional study was conducted in an educational laboratory setting involving twenty-two ATs (age 36.7±10.8 years; 13 males, …

Use Of Telemedicine In A Sports Medicine Clinic: An Investigation Of Patient Satisfaction, Kelly Harrington, Lindsey E. Eberman, Matthew J. Rivera, J'Nai Pittman, Shelby Broughton, Regina Hash

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

Objective: Compare patient satisfaction between telemedicine and in-office visits and between providers post-operatively in an orthopedics setting with athletic trainers and physicians.

Design: Cross-sectional study

Methods: Patients from a Sports Medicine Clinic that received an orthopedic surgical intervention from March 2020-September 2021, and engaged in telemedicine, or an in-office visit post-operatively. Provider type included full-time athletic trainers, resident athletic trainers, physician (MD) resident/fellows, and float athletic trainers. Press-Ganey Patient Experience Surveys were collected at the time of follow up visit, with focus on items, “likelihood to recommend” and “how well staff worked together.”

Results: There was a total of 255 …

Telehealth Education In Athletic Training, W. David Carr, Mccall E. Christian, Jennifer L. Volberding, Zachary K. Winkelmann

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

Context: Within the broad telehealth education literature, there are numerous case studies and position statements from various associations of model practices. Little is known about how athletic training is addressing telehealth education. Objective: To determine how athletic training education programs teach, assess, and structure telehealth content. Design: Cross-sectional study Setting: Online survey instrument Patients or Other Participants: An institutional athletic training faculty member from 82 athletic training programs in the United States. Data Collection and Analysis: The survey contained the validated Telehealth Evaluative Content in Higher Education (TECHE) instrument, which consisted of descriptive items focused on how education programs teach, …

Athletic Training Students’ Experiences And Perceptions Of Exertional Heat Stroke Simulated Encounters: A Qualitative Analysis, Hannah L. Stedge, Malissa Martin, Beth L. Kinslow, Valerie Herzog, Christine Reyes

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

Introduction: Athletic trainers are trained to recognize exertional heat stroke (EHS), which is critical to implementing lifesaving measures. Rectal thermometry is the best practice for recognizing EHS, and the Commission on Accreditation of Athletic Training Education (CAATE) requires students to learn rectal thermometry. Rooted in transformative learning theory, this study explored the perceptions and experiences of athletic training students following simulated EHS encounters with either high-fidelity (HF) simulators or standardized patients (SPs). Methods: This was a qualitative study using phenomenological theory. Through semi-structured qualitative interviews, we explored participants' personal experiences and perceptions following their simulation interventions. Participants included sixteen first-year …

“How Much Time Do I Have Left?”: Lessons From Rapid City Hospice, Hannah Meyer, Oluwafunke Oluwatosin Ogunremi

Sanford School of Medicine Cultural Immersion & Service Learning

From August 21st-23rd we spent our days at the Monument Health Home + Hospice House in Rapid City. The goal was to learn more about hospice care, and the attitude around it.

Sars-Cov-2 Infection Induces Human Milk Antibodies Capable Of Mediating Multiple Functional Activities, Jared Sheehan, Aline Andres, Laxmi Yeruva, Alistair J. Ramsay

School of Medicine Faculty Publications

Background and Aims: Passive transfer of antibodies through breastfeeding is a potential mode of protection for newborns and infants following maternal SARS-CoV-2 infection. The primary goal of this study was to evaluate and characterize SARS-CoV-2 Spike (S)-specific antibodies in human milk samples collected longitudinally from a cohort of convalescent mothers. Methods: SARS-CoV-2 infected participants enrolled in this study were lactating women aged 29–36 years with a confirmed COVID-19 diagnosis who donated milk samples at intervals over the six-month study period. Samples were evaluated for antibody subclass SARS-Cov-2 S glycoprotein binding activity by ELISA, and for the capacity of antibodies purified …

Neuregulin1 Nuclear Signaling Influences Adult Neurogenesis And Regulates A Schizophrenia Susceptibility Gene Network Within The Mouse Dentate Gyrus, Prithviraj Rajebhosale, Alice Jone, Kory R Johnson, Rohan Hofland, Camille Palarpalar, Samara Khan, Lorna W Role, David A Talmage

Faculty, Staff and Student Publications

Neuregulin1 (Nrg1) signaling is critical for neuronal development and function from fate specification to synaptic plasticity. Type III Nrg1 is a synaptic protein which engages in bidirectional signaling with its receptor ErbB4. Forward signaling engages ErbB4 phosphorylation, whereas back signaling engages two known mechanisms: (1) local axonal PI3K-AKT signaling and (2) cleavage by γ-secretase resulting in cytosolic release of the intracellular domain (ICD), which can traffic to the nucleus (Bao et al., 2003; Hancock et al., 2008). To dissect the contribution of these alternate signaling strategies to neuronal development, we generated a transgenic mouse with a missense mutation (V

Personalized Copd Care: The Future Of Precision-Based Therapies, Leslie K Appleton, Nicola A Hanania, Muhammad Adrish

Faculty, Staff and Students Publications

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory illness characterized by long-standing respiratory symptoms and airflow limitation. It is a major contributor to respiratory disease-related deaths and currently ranked as the sixth leading cause of mortality in the United States. Approved pharmacological therapies for the stable disease primarily consist of inhaled short and long-acting bronchodilators, inhaled corticosteroids, azithromycin, and roflumilast. In recent years, significant progress has been made in the management of COPD through the identification of different COPD phenotypes and endotypes, which allows for a more personalized treatment approach. While earlier studies investigating targeted therapies were less promising, …

Therapeutic Approaches To Modulate The Immune Microenvironment In Gliomas, Andreas Sarantopoulos, Chibawanye Ene, Elisa Aquilanti

Faculty, Staff and Student Publications

Immunomodulatory therapies, including immune checkpoint inhibitors, have drastically changed outcomes for certain cancer types over the last decade. Gliomas are among the cancers that have seem limited benefit from these agents, with most trials yielding negative results. The unique composition of the glioma immune microenvironment is among the culprits for this lack of efficacy. In recent years, several efforts have been made to improve understanding of the glioma immune microenvironment, aiming to pave the way for novel therapeutic interventions. In this review, we discuss some of the main components of the glioma immune microenvironment, including macrophages, myeloid-derived suppressor cells, neutrophils …

Impact Of Select Actionable Genomic Alterations On Efficacy Of Neoadjuvant Immunotherapy In Resectable Non-Small Cell Lung Cancer, Nicolas Zhou, Cheuk H Leung, William N William, Annikka Weissferdt, Apar Pataer, Myrna C B Godoy, Brett W Carter, Frank V Fossella, Anne S Tsao, George R Blumenschein, Xiuning Le, Jianjun Zhang, Ferdinandos Skoulidis, Jonathan M Kurie, Mehmet Altan, Charles Lu, Bonnie S Glisson, Lauren A Byers, Yasir Y Elamin, Reza J Mehran, David C Rice, Garrett L Walsh, Wayne L Hofstetter, Jack A Roth, Hai T Tran, Jia Wu, Luisa M Solis Soto, Humam Kadara, Stephen G Swisher, Ara A Vaporciyan, Don L Gibbons, Heather Y Lin, J Jack Lee, John V Heymach, Marcelo V Negrao, Boris Sepesi, Tina Cascone

Faculty, Staff and Student Publications

Background: Neoadjuvant immune checkpoint inhibitors (ICIs) have improved survival outcomes compared with chemotherapy in resectable non-small cell lung cancer (NSCLC). However, the impact of actionable genomic alterations (AGAs) on the efficacy of neoadjuvant ICIs remains unclear. We report the influence of AGAs on treatment failure (TF) in patients with resectable NSCLC treated with neoadjuvant ICIs.

Methods: Tumor molecular profiles were obtained from patients with stage I-IIIA resectable NSCLC (American Joint Committee on Cancer seventh edition) treated with either neoadjuvant nivolumab (N, n=23) or nivolumab+ipilimumab (NI, n=21) followed by surgery in a previously reported phase-2 randomized study (NCT03158129). TF …

The Dleu2/Mir-15a/Mir-16-1 Cluster Shapes The Immune Microenvironment Of Chronic Lymphocytic Leukemia, Ronghua Zhang, Priyanka Khare, Priyanka Banerjee, Cristina Ivan, Sarah Schneider, Federica Barbaglio, Karen Clise-Dwyer, Vanessa Behrana Jensen, Erika Thompson, Marisela Mendoza, Nicholas Chiorazzi, Shih-Shih Chen, Xiao-Jie Joy Yan, Nitin Jain, Paolo Ghia, Federico Caligaris-Cappio, Rima Mendonsa, Sashi Kasimsetty, Ryan Swoboda, Recep Bayraktar, William Wierda, Varsha Gandhi, George A Calin, Michael J Keating, Maria Teresa Sabrina Bertilaccio

Faculty, Staff and Student Publications

The development and progression of chronic lymphocytic leukemia (CLL) depend on genetic abnormalities and on the immunosuppressive microenvironment. We have explored the possibility that genetic drivers might be responsible for the immune cell dysregulation that shapes the protumor microenvironment. We performed a transcriptome analysis of coding and non-coding RNAs (ncRNAs) during leukemia progression in the Rag2-/-γc-/- MEC1-based xenotransplantation model. The DLEU2/miR-16 locus was found downmodulated in monocytes/macrophages of leukemic mice. To validate the role of this cluster in the tumor immune microenvironment, we generated a mouse model that simultaneously mimics the overexpression of hTCL1 and the germline deletion of the …