Digital Commons Network^™

Subcutaneous Insulin Use In Diabetic Ketoacidosis, Patrick Mcgrath

Lynchburg Journal of Medical Science

The reviewed literature focuses on the clinical application of subcutaneous (SQ) insulin, particularly rapid-acting insulin analogs (RAIAs), in treating selected patients with mild to moderate diabetic ketoacidosis (DKA). The use of SQ insulin offers a viable alternative to traditional intravenous (IV) insulin infusions, enabling DKA management outside intensive care unit (ICU) settings and reducing healthcare resource utilization. Current DKA management protocols emphasize comprehensive fluid resuscitation and correction of electrolyte imbalances, with IV regular insulin administered at 0.1 units/kg/hour. This review synthesizes findings from multicenter cohort studies, meta-analyses, and randomized controlled trials (RCTs) available via PubMed, focusing on adult patients diagnosed …

Genetic Adaptations And Malaria Prophylaxis In Sickle Cell Disease: Reducing Morbidity And Mortality, Fuseina Gimballa

Lynchburg Journal of Medical Science

This study examines the relationship between sickle cell disease (SCD) and malaria, focusing on the benefits and risks of the sickle cell trait, complications associated with SCD, and the impact of malaria infection in endemic regions. The paper emphasizes the importance of antimalarial prophylaxis for patients with SCD living in these areas. Evidence suggests a genetic adaptation in populations exposed to malaria, where a β-globin mutation provides partial protection against infection in individuals with the sickle cell trait. Studies consistently show that heterozygous carriers are largely protected from severe malaria, whereas individuals with homozygous SCD remain highly susceptible, resulting in …

Brief Overview Of Assessment And Prognostication Tools For Palliative Care Oncology Patients, Nicole Schwensow

Lynchburg Journal of Medical Science

Patients with life-threatening illnesses can be at risk for the progression of their disease over time. Consequences of such an illness can include recurrent hospitalizations, poor symptom control, and a lack of understanding by the patient and family of the disease, its usual course, and prognosis. Palliative care is a philosophy of care intended to address these issues. While receiving palliative care, patients can continue to undergo treatments directed at a cure, whereas hospice patients no longer receive treatment for underlying diseases. Both approaches focus on symptom control. To best care for palliative patients over time, several outcome domains should …

Management Of Difficult Patient Situations, Sangeetha Larsen Mpas, Pa-C

Lynchburg Journal of Medical Science

The purpose of this paper is to provide strategies for clinicians to manage difficult patient interactions. A comprehensive search of PubMed was conducted, identifying articles that identified the root cause of difficult patient interactions and assessed methods for successfully navigating these situations. The term “difficult patient” reflects the interaction of patient behavior, clinician perception, and systemic constraints rather than an inherent patient flaw. Effective management involves reframing difficult behavior as an expression of unmet needs and responding with empathy, active listening, clear boundaries, and collaborative decision-making. System-level strategies reduce patient distress and clinician burnout. Ultimately, the difficult patient represents strained …

Physician Assistants And The Medical Science Liaison Role: Expanding Career Pathways Beyond Clinical Practice, Michael Filsinger

Lynchburg Journal of Medical Science

ABSTRACT

The purpose of this article is to examine how physician assistants can transition into Medical Science Liaison roles within the pharmaceutical and biotechnology industries. Growing interest in nonclinical career pathways has prompted more physician assistants to explore opportunities in medical affairs, yet many remain uncertain about the qualifications, expectations, and academic preparation associated with these positions. A focused literature review was conducted to evaluate the competencies required for Medical Science Liaison roles, the barriers clinician applicants often encounter, and the strategies that may support successful transition into industry-based careers. Findings show that physician assistants possess relevant strengths such as …

Understanding Monoclonal Gammopathy Of Undetermined Significance, Scott Winkel Msph, Mhs, Pa-C

Lynchburg Journal of Medical Science

Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma cell disorder characterized by serum monoclonal protein (M-protein) levels less than 3.0 g/dL, less than 10% plasma cells in the bone marrow, and absence of end-organ damage. It mainly affects older adults and is often an incidental finding. While most cases remain indolent, a subset progresses to malignancies such as multiple myeloma, smoldering myeloma, AL amyloidosis, lymphoproliferative disorders, macroglobulinemia, and monoclonal gammopathy of renal significance. This review summarizes current insights into MGUS pathophysiology, risk factors, molecular mechanisms, clinical features, diagnostic approaches, including laboratory assessments and imaging, and emphasizes early detection …

Forever Un-Wild: How The Forever Wild Clause “Locks Up” New York’S Closed Correctional Facilities, William Carswell

Pace Environmental Law Review

Article XIV of the New York State Constitution, better known as the “Forever Wild Clause,” enshrines a conservationist ideal into law. The crux of article XIV prohibits the leasing, selling, or exchanging of state-owned land within New York’s Forest Preserve to private entities. Since its inception, this mandate has dictated the State’s approach to management of its Forest Preserve. Whenever New York decides to excise a piece of its Forest Preserve, the cumbersome yet necessary constitutional amendment process is triggered. Renewed attention to this legal requirement is peaking. Since 2009, five former Department of Corrections and Community Supervision sites located …

Surf And Turf: How Litigation Against Concentrated Animal Feeding Operations Can Inform Regulation Of The Aquaculture Industry, Amanda Kapitula

Pace Environmental Law Review

Industrial agriculture dominates the U.S. agricultural industry. On land, animals are stuffed into factory-like facilities, called concentrated animal feeding operations (“CAFOs”), where they are raised to maximize the output of food products. In the process, they produce vast amounts of waste, contaminating surrounding air and water resources. Increasingly, factory farms are making their way into the water as the fishing industry shifts from wild-catch systems to aquaculture operations, or the raising of fish for consumption. While aquaculture has the potential to be a more sustainable option than both wild-catch and animal agriculture, concentrated aquatic animal production facilities (“CAAPFs”) also have …

Climate Preemption And Fossil Fuel Entrenchment, Vincent Nolette

Pace Environmental Law Review

Mitigating the worst impacts of climate change demands a rapid reduction in greenhouse gas emissions and a transition to renewable, low-carbon sources of energy. This requires building thousands of gigawatts of clean energy at an unprecedented rate and expeditiously retiring existing fossil fuel infrastructure. Yet both parts of this task have been obstructed by state legislative efforts over the last decade—particularly in Republican-led states—to block local governments from reducing greenhouse gas emissions while legally mandating continued fossil fuel reliance. These efforts are accomplished through state climate preemption laws. Framed in neutral or positive terms like “energy choice,” the actual effect …

Models Of Care In Higher Education: Comparing Integrated And Standalone Approaches To Student Mental Health, Tevia Q. Strand

The Interactive Journal of Global Leadership and Learning

This qualitative study examines how the organization of campus mental health services—integrated, co-located care versus standalone counseling centers—shapes college students’ awareness, access, stigma/privacy, and engagement. Semi-structured interviews with five Midwestern undergraduate women (n = 5) explored perceptions of visibility, ease of use, barriers, and improvement ideas. Transcripts were analyzed using reflexive thematic analysis. Themes included confusion about entry pathways, visibility-related stigma, and the salience of faculty/peer bridges to services. Students generally preferred integrated models, citing privacy through co-location, normalization, and easier warm handoffs; some noted that standalone centers can feel more specialized yet risk heightened visibility depending on location. Findings …

Redefining Rural School Leadership In The Post-Pandemic Era: Lessons From Covid-19, Brennan Kent

The Interactive Journal of Global Leadership and Learning

The COVID-19 pandemic fundamentally reshaped educational leadership, especially in rural school settings where leaders confronted unique resource constraints, geographic isolation, and heightened community interdependence. This conceptual study reexamines rural educational leadership in the post-pandemic era through a synthesis of findings from Author’s (2023) dissertation, The Rural Education Leadership Experience Amid the COVID-19 Pandemic, and current leadership theory. Drawing on the McREL Balanced Leadership Framework alongside adaptive and servant leadership models, the analysis identifies four interrelated dimensions that define post-pandemic rural leadership: communication as community cohesion, relationships as infrastructure, adaptive leadership as necessity, and well-being as a leadership priority. These …

Voices From The Hyflex Classroom: Understanding The Graduate Counseling Student Experience, Taryn Akgul, Jessica Brown, Aaron Suomala Folkerds

The Interactive Journal of Global Leadership and Learning

Counselor education and counseling master’s Programs face a changing landscape in higher education. This includes balancing the demand for a high-quality HyFlex program that prepares students for the counseling field. This qualitative exploratory study utilized a phenomenological approach to understand the counseling master's student experience in a hybrid program. The research questions focused on the students' experience attending the program either strictly on zoom, in person, or a combination of both and how that impacted them and their learning. The study consisted of eight participants who were alumni from one CACREP accredited counseling masters program. The findings included themes of …

State Of California Cannabis Reporting, University Of Mississippi – National Center For Cannabis Research And Education

California

No abstract provided.

Effect Of Remineralization And Resin Infiltration On Microhardness, Mineral Content And Cervical Microleakage Of Restored Demineralized Enamel, Sara Adel Botros, Caroline Maged Massieh

Dentistry

No abstract provided.

Technology-Enabled Cognitive Behavioral Therapy For Insomnia (Cbt-I) In Older Adults With Mild Cognitive Impairment: Development And Feasibility Study, Hongtu Chen, Marta Pagán-Ortiz, Sara Romero Vincente, Emma Chapman, James Maxwell, Otis L. Owens, Sue E. Levkoff Scd, Msw, Sm

Faculty and Staff Publications

Background/Objectives: Mild Cognitive Impairment (MCI) is a transitional stage between normal aging and early dementia, affecting up to 20% of older adults. Sleep disturbances, particularly insomnia, affect around 60% of individuals with MCI, contributing to declines in cognitive and physical function. Although Cognitive Behavioral Therapy for Insomnia (CBT-I) is an evidence-based non-pharmacological treatment, few studies have adapted it for individuals with MCI. This pilot study developed and evaluated Slumber, a clinician-supported mobile CBT-I app tailored for older adults with MCI and insomnia. Methods: The study had three aims: (1) to develop the app for delivering CBT-I to individuals with …

The Computationally Designed Tri2-2 Miniprotein Inhibitor Protects Against Multiple Sars-Cov-2 Omicron Variants, Jimin Lee, James Brett Case, Young-Jun Park, Rashmi Ravichandran, Daniel Asarnow, M Alejandra Tortorici, Jack T Brown, Shilpa Sanapala, Lauren Carter, David Baker, Michael S Diamond, David Veesler

2020-Current year OA Pubs

The continued evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has compromised neutralizing antibody responses elicited by prior infection or vaccination and abolished the utility of most monoclonal antibody therapeutics. We previously described a computationally-designed, homotrimeric miniprotein inhibitor, designated TRI2-2, that protects mice against pre-Omicron SARS-CoV-2 variants. Here, we show that TRI2-2 exhibits broadly neutralizing activity of SARS-CoV-2 variants and protects mice against BQ.1.1, XBB.1.5 and BA.2.86 challenge when administered intranasally post-exposure. The resistance of TRI2-2 to viral escape by most variants and the ability to deliver it directly to the upper airways highlight the potential of the multivalent …

Comparing Power Outputs Of A Jump Shrug With A Hex Bar Vs A Straight Bar, Joshua Neumann

Doctorate in Kinesiology

The purpose of this dissertation was to examine whether barbell selection influenced power outputs during loaded jump shrugs in collegiate athletes and to connect research findings to practical applications in strength and conditioning. Although Trap Bars are often assumed to provide mechanical advantages during explosive lifts, limited research has evaluated their impact during ballistic derivatives such as jump shrugs. This study addressed that gap by comparing the performance of Straight Bar and Trap Bar exercises across four standardized loads in male and female Division II athletes. A repeated-measures design was used to assess barbell velocity, concentric mean power, peak landing …

Real-World Data Investigating The Frequency Of Flash Glucose Monitoring And Glycaemic Metrics In Omani Diabetes Patients: A Preliminary Retrospective Cross-Sectional Study, Ammar Al-Mamari, Sumaia Al Gharabi, Merah Al Busaidy, Abdulla Al Futaisi

Sultan Qaboos University Medical Journal

Objectives: This study aimed to evaluate real-world glycaemic outcomes associated with flash glucose monitoring (FGM) use in patients with diabetes at Sultan Qaboos University Hospital, Muscat, Oman. Methods: This retrospective cross-sectional study was conducted among diabetic patients using flash glucose monitoring between January 2022 and August 2023. Patients were grouped by scanning frequency, time-in-range (TIR) and estimated A1c (eA1c). Associations between scanning frequency and glycaemic metrics were analysed. Results: A total of 436 patients were included in this study. Patients with higher scanning frequency (≥12 scans/day, median = 17) achieved greater TIR (52.4% versus 34.8%), lower time-above-range (41.8% versus 57.0%), …

Large-Scale Blood Pressure Gwas Accounting For Gene-Depression Interactions In 564,680 Individuals From Diverse Populations, Songmi Lee, Clint L Miller, Amy R Bentley, Michael R Brown, Pavithra Nagarajan, Raymond Noordam, John L Morrison, Karen Schwander, Kenneth Westerman, Minjung Kho, Aldi T Kraja, Paul S De Vries, Farah Ammous, Hughes Aschard, Traci M Bartz, Anh Do, Charles T Dupont, Mary F Feitosa, Valborg Gudmundsdottir, Xiuqing Guo, Sarah E Harris, Keiko Hikino, Zhijie Huang, Christophe Lefevre, Leo-Pekka Lyytikäinen, Yuri Milaneschi, Giuseppe Giovanni Nardone, Aurora Santin, Helena Schmidt, Botong Shen, Tamar Sofer, Quan Sun, Ye An Tan, Jingxian Tang, Sébastien Thériault, Peter J Van Der Most, Erin B Ware, Stefan Weiss, Wang Ya Xing, Chenglong Yu, Wei Zhao, Md Abu Yusuf Ansari, Pramod Anugu, John R Attia, Lydia A Bazzano, Joshua C Bis, Max Breyer, Brian Cade, Guanjie Chen, Stacey Collins, Janie Corley, Gail Davies, Marcus Dörr, Jiawen Du, Todd L Edwards, Tariq Faquih, Jessica D Faul, Alison E Fohner, Amanda M Fretts, Srushti Gangireddy, Adam Gepner, Mariaelisa Graff, Edith Hofer, Georg Homuth, Michelle M Hood, Xu Jie, Mika Kähönen, Sharon L R Kardia, Carrie A Karvonen-Gutierrez, Lenore J Launer, Daniel Levy, Maitreiyi Maheshwari, Lisa W Martin, Koichi Matsuda, John J Mcneil, Ilja M Nolte, Tomo Okochi, Laura M Raffield, Olli T Raitakari, Lorenz Risch, Martin Risch, Ana Diez Roux, Edward A Ruiz-Narvaez, Tom C Russ, Takeo Saito, Pamela J Schreiner, Rodney J Scott, James Shikany, Jennifer A Smith, Harold Snieder, Beatrice Spedicati, E Shyong Tai, Adele M Taylor, Kent D Taylor, Paola Tesolin, Rob M Van Dam, Rujia Wang, Wei Wenbin, Tian Xie, Jie Yao, Kristin L Young, Ruiyuan Zhang, Alan B Zonderman, Biobank Japan Project, Lifelines Cohort Study, Maria Pina Concas, David Conen, Simon R Cox, Michele K Evans, Ervin R Fox, Lisa De Las Fuentes, Ayush Giri, Giorgia Girotto, Hans J Grabe, Charles Gu, Vilmundur Gudnason, Sioban D Harlow, Elizabeth Holliday, Jonas B Jost, Paul Lacaze, Seunggeun Lee, Terho Lehtimäki, Changwei Li, Ching-Ti Liu, Alanna C Morrison, Kari E North, Brenda W J H Penninx, Patricia A Peyser, Michael M Province, Bruce M Psaty, Susan Redline, Frits R Rosendaal, Charles N Rotimi, Jerome I Rotter, Reinhold Schmidt, Xueling Sim, Chikashi Terao, David R Weir, Xiaofeng Zhu, Nora Franceschini, Jeffrey R O'Connell, Cashell E Jaquish, Heming Wang, Alisa Manning, Patricia B Munroe, Dabeeru C Rao, Han Chen, W James Gauderman, Laura J Bierut, Thomas W Winkler, Myriam Fornage

Faculty, Staff and Student Publications

Gene-environment interactions may enhance our understanding of blood pressure (BP) biology. We conducted a meta-analysis of multi-population genome-wide association studies (GWASs) of BP traits accounting for gene-depressive symptomatology (DEPR) interactions. Our study included 564,680 adults from 67 cohorts and four population backgrounds: African (5%), Asian (7%), European (85%), and Hispanic (3%). We discovered seven previously unreported BP loci showing gene-DEPR interaction. These loci mapped to genes implicated in neurogenesis (TGFA and CASP3), lipid metabolism (ACSL1), neuronal apoptosis (CASP3), and synaptic activity (CNTN6 and DBI). We also showed evidence for gene-DEPR interaction at nine known BP loci, further suggesting links between …

Secure Distributed Multiple Imputation Enables Missing Data Inference For Private Data Proprietors, Haris Smajlović, Yi Lian, Qi Long, Ibrahim Numanagić, Xiaoqian Jiang

Faculty, Staff and Student Publications

Scattered between many healthcare providers across the US, Electronic Health Records (EHR) are extensively used for research purposes. Collaboration and sharing of EHRs between multiple institutions often provide access to more diverse datasets and a chance to conduct comprehensive studies. However, these collaboration efforts are usually hindered by privacy issues that render the pooling of such data at a centralized database impossible. Furthermore, EHRs are often incomplete and require statistical imputation prior to the study. To enable collaborative studies on top of incomplete, private EHRs, here we provide a provably secure solution built with secure multiparty computation (SMC) that provides …

Association Of Neighborhood Economic Trajectories And Risk Of Mortality Among Older Adults, Erika Figueroa-Solis, Qian Xiao

Faculty, Staff and Student Publications

Background

Lower neighborhood socioeconomic status (SES) and decline in neighborhood SES have been linked to detrimental health outcomes, such as cardiovascular disease (CVD), cancer, and mortality. However, few studies have investigated distinct types of neighborhood economic trajectories in relation to mortality. We examined the association between the recently developed multidimensional measure of neighborhood trajectories and mortality in older adults enrolled in the National Institutes of Health-AARP Diet and Health Study (NIH-AARP).

Methods

Neighborhoods were classified into five groups based on economic change patterns from 2000 to 2016 using American Community Survey data: Stability, Growth, Displacement, Abandonment, and Poverty Concentration. Mortality …

Characteristics And Effectiveness Of Maternal Health Interventions To Prevent Mother-To-Child Transmission (Pmtct) Of Syphilis In A Global Setting: A Scoping Review Using Intervention Mapping As A Framework, Jinni Tang, Anusha Sajja, Christine Markham, Emily T Hebert, Irene Stafford, Sheryl Dacso, Melissa F Peskin

Faculty, Staff and Student Publications

Background: Despite the availability of cost-effective treatments, maternal syphilis continues to contribute significantly to preventable stillbirths and congenital syphilis cases worldwide. This scoping review aimed to identify and characterize maternal health interventions designed to prevent mother-to-child transmission (PMTCT) of syphilis globally, using a modified Intervention Mapping (IM) framework.

Methods: We conducted a scoping review of maternal health interventions targeting PMTCT of syphilis published between January 2010 and August 2023. Searches were performed in PubMed, Medline Ovid, and Embase, supplemented by manual reference screening. Eligible studies described at least one maternal health intervention addressing syphilis PMTCT and were analyzed using a …

Flipi24: A Modern Prognostic Model And Clinical Trial Enrichment Tool For Newly Diagnosed Follicular Lymphoma, Matthew J Maurer, Vit K Prochazka, Tarec Christoffer El-Galaly, Christopher R Flowers, Diego Villa, Emmanuel Bachy, Elliot J Cahn, Marguerite Fournier, Melissa C Larson, Caroline E Dietrich, Lasse Hjort Jakobsen, Hervé Ghesquières, Robert Kridel, Maher K Gandhi, Chan Y Cheah, Eliza A Hawkes, John F Seymour, Ciara L Freeman, Michael R Clausen, Björn E Wahlin, Jonathan W Friedberg, Carla Casulo, Thomas M Habermann, Yucai Wang, Loretta J Nastoupil, Peter De Nully Brown, David Belada, Andrea Janíková, Heidi Mocikova, Tomáš Fürst, Pierre Feugier, Hervé Tilly, Corinne Haioun, Andrew J Davies, Guillaume Cartron, Richard Burack, Dai Chihara, Peter Martin, Jonathon B Cohen, Izidore S Lossos, Brad S Kahl, Laurie H Sehn, Karin E Smedby, Gilles Salles, Marek Trneny, Brian K Link, Franck Morschhauser, James R Cerhan

Faculty, Staff and Student Publications

Purpose: Although most patients with follicular lymphoma (FL) can expect an indolent course, progressive lymphoma remains the primary cause of death during the first decade after diagnosis. Progression of disease within 24 months (POD24) of starting first-line (1L) immunochemotherapy defines a high-risk population with poor survival, but better risk stratification at diagnosis is needed.

Methods: The FLIPI24 model was developed and internally validated to predict 24-month event rates using individual data from 4,485 patients treated with 1L immunochemotherapy from 10 observational cohorts of FL. Overall and cause-specific survival was further evaluated in FLIPI24 risk groups. External validation in the 1L …

Identification Of Cadm1 As An Immunotherapeutic Target And Evaluation Of A Novel Cadm1-Targeting Antibody-Drug Conjugate In Preclinical Osteosarcoma Models, Yifei Wang, Zhongting Zhang, Caterina Longo, Wendong Zhang, Qi Wang, Amer Najjar, Xiangjun Tian, Rossana N Lazcano Segura, Michael E Roth, Jonathan Gill, Douglas J Harrison, Zhaohui Xu, Yanhua Yi, Xin Zhou, Sylvester Jusu, Timothy M Stearns, Steven B Neuhauser, Carol J Bult, Jing Wang, Alexander J Lazar, Richard Gorlick

Faculty, Staff and Student Publications

Due to the paucity of validated cell surface osteosarcoma-specific targets, patients with this condition have long been excluded from the benefits of antibody-drug conjugate (ADC) therapy observed in patients with several solid and hematologic malignancies. Our comprehensive surfaceome profiling approach previously identified osteosarcoma-specific cell-surface antigens that are highly expressed in osteosarcomas but minimally expressed in normal tissues. As a result, one such antigen, CADM1, was selected for the generation of an ADC. We tested a CADM1-targeting ADC with a tesirine payload (SG3249) in vitro in osteosarcoma, rhabdomyosarcoma, and neuroblastoma patient-derived xenograft cell lines. In vivo, we tested six CADM1-expressing osteosarcoma …

Financial Ratios And Stock Volatility: Empirical Evidence From The Banking Sector, Rahma Tri Benita

Journal of Accounting Auditing and Business

Banking stock price volatility is closely related to company performance and fundamental indicators. This study analyzes the short-term and long-term relationships between financial ratios and stock price volatility in the banking sector. Based on the results of the long-term correlation, the Price to Earnings Ratio (P/E) and Dividend Yield (DY) variables are proven to be dominant factors influencing volatility because they are directly related to stock price movements. In the short-term correlation between state-owned banks, there is an inverse relationship between Price to Book and ROE, and Debt to Equity has a significant negative effect on Return on Assets and …

Unravelling Impact Of Comorbidities On Mortality Risks In Ckd Patients During The Covid-19 Pandemic: An Explainable Ai-Driven Study, Zeinab Abdollahi, Lin Huo, Donald Fraser, Shang-Ming Zhou

School of Nursing and Midwifery

ObjectivesThe chronic kidney disease (CKD) patients were at high risk for severe clinical complications during the COVID-19 pandemic. Our objectives were to evaluate comorbidity prevalence; predict mortality risks for CKD patients during the pandemic; assess how various health factors interact to influence mortality; and provide insights for targeted prevention strategies.MethodWe analysed data from 186,396 CKD patients in Mexico during the entire pandemic (Jan 2020- May 2023). Explainable artificial intelligence (XAI) methods with extreme gradient boosting (XGBoost) models and Shapley Additive Explanations (SHAP) were developed to predict mortality for CKD patients with model interpretations. Different metrics were used to comprehensively evaluate …

Proton Versus Photon Radiotherapy For Patients With Oropharyngeal Cancer In The Usa: A Multicentre, Randomised, Open-Label, Non-Inferiority Phase 3 Trial, Steven J Frank, Paul M Busse, J Jack Lee, David I Rosenthal, Mike Hernandez, David M Swanson, Adam S Garden, G Brandon Gunn, Samir H Patel, James W Snider, Daniel J Ma, Jason K Molitoris, Nancy Y Lee, Upendra Parvathaneni, Mark W Mcdonald, Noah S Kalman, Alexander Lin, Nasiruddin Mohammed, Christina Henson, Christian Hyde, Gopal K Bajaj, Sanford R Katz, Roi Dagan, William H Morrison, Jay P Reddy, C David Fuller, Shalin J Shah, Jack Phan, Gregory M Chronowski, Lauren Mayo, Erich M Sturgis, Renata Ferrarotto, Xiaorong R Zhu, Xiaodong Zhang, Li Wang, Katherine A Hutcheson, Adel K El-Naggar, Amy C Moreno, Anna Lee, Michael T Spiotto, Neil D Gross, Stephen Y Lai, Jay J Liao, Jonathan Paly, Zhongxing Liao, Robert L Foote

Faculty, Staff and Student Publications

Background: Radiotherapy is an integral component of treatment for oropharyngeal cancer. Toxicity from the current state-of-the-art photon radiotherapy, intensity-modulated radiation therapy (IMRT), has prompted the search for alternative, less toxic therapies. One such alternative that might de-intensify treatment is proton therapy. In this trial, we aimed to directly compare IMRT with intensity-modulated proton therapy (IMPT), both concurrent with systemic therapy, hypothesising comparable disease control and survival and lower toxicity.

Methods: This randomised, multicentre, open-label, non-inferiority, phase 3 trial was conducted in 21 sites (cancer centres or universities) in the USA. Patients (aged ≥18 years) with stage III or stage IV …

Il-18 Metabolically Reprograms Car-Expressing Natural Killer T Cells And Enhances Their Antitumor Activity, Gabriel A Barragán Bravo, David A De La Cerda, Elisa Landoni, Kshiti Dholakia, Piotr Humeniuk, Leidy D Caraballo Galva, Ying Wang, Gengwen Tian, Boning Yang, Linjie Guo, Michael S Wood, Xavier Rios, Xin Xu, Amy N Courtney, Erica J Di Pierro, Joan Jacob, Yi-Han Li, Akshaya Adaikkalavan, Norihiro Watanabe, Sufeng Mao, George Miles, Gianpietro Dotti, Leonid S Metelitsa

Faculty, Staff and Students Publications

Invariant natural killer T cells (NKTs) have intrinsic anti-tumor properties that make them promising candidates for chimeric antigen receptor (CAR) immunotherapies. Transgenic cytokine expression can enhance cellular therapy potency, and we hypothesized that co-expressing IL-18 alone or with IL-15 would boost CAR-NKT therapeutic potential. To test this, we generated retroviral constructs expressing IL-15 and/or IL-18 with an inducible caspase 9 safety switch and co-transduced them with a GD2-specific CAR into human NKTs. Co-expression of IL-18 or IL-15/IL-18 increased CAR-NKT cytotoxicity, proliferation, and cytokine secretion in vitro compared to IL-15 alone. IL-18 also enhanced GPC3.CAR and CD19.CAR NKT activity against hepatocellular …

Plasma Proteomics And Incident Coronary Heart Disease, Matthew P Huber, Jennifer A Brody, Colleen M Sitlani, Thomas R Austin, Usman A Tahir, Shuliang Deng, Devendra Meena, Jingsha Chen, Kunihiro Matsushita, Christie M Ballantyne, Josef Coresh, Robert E Gerszten, Russell P Tracy, Ting Ye, Bruce M Psaty, Joshua C Bis, James S Floyd

Faculty, Staff and Students Publications

Background: Systematic profiling of plasma proteins in population studies offers a complementary approach to discovery of novel risk factors and may provide new insights into the causes of coronary heart disease.

Methods: To explore relationships between the circulating proteome and coronary heart disease (CHD), we evaluated associations of 4780 plasma proteins with incident CHD in the Cardiovascular Health Study (CHS, N=2856, 575 CHD events) and replicated significant associations in the Atherosclerosis Risk in Communities Study (ARIC, N = 10456; 1375 events).

Results: We find that 11 proteins significantly associate with incident CHD after adjusting for risk factors; and eight significantly …

Transcriptomic Signature-Guided Depletion Of Intermediate Alveolar Epithelial Cells Ameliorates Pulmonary Fibrosis In Mice, Fei Peng, Chun-Sun Jiang, Zhen Zheng, Shahram Aliyari, Dan Shan, Aaryan Sabharwal, Qinyan Yin, Shigeki Saito, Chao He, Ivan O Rosas, Joseph A Lasky, Victor J Thannickal, Yong Zhou

Faculty, Staff and Students Publications

Single-cell RNA sequencing (scRNA-seq) has identified intermediate epithelial states in pulmonary fibrosis, including KRT5-/KRT17+ aberrant basaloid cells in humans and Krt8+ alveolar differentiation intermediates (ADIs) in mice. Their functional contributions to fibrogenesis, however, remain unclear. Here, we introduce an RNA-sensing-dependent protein translation technology that enables selective targeting of Krt8+ ADI cells in vitro and in vivo. Transcriptomic analysis revealed Small Proline-Rich Protein 1 A (SPRR1A) mRNA as a shared marker of murine Krt8+ ADIs and human KRT5-/KRT17+ basaloid cells, distinguishing them from other lung cell populations. Using programmable RNA sensors, we demonstrated selective EGFP-labeling of Krt8+ ADI cells in vivo, …