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Dual Targeting Of Cd19 And Cd22 With Bicistronic Car-T Cells In Patients With Relapsed/Refractory Large B-Cell Lymphoma, Claire Roddie, Nancy Bartlett, Et Al. May 2023

Dual Targeting Of Cd19 And Cd22 With Bicistronic Car-T Cells In Patients With Relapsed/Refractory Large B-Cell Lymphoma, Claire Roddie, Nancy Bartlett, Et Al.

2020-Current year OA Pubs

Relapse after CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy for large B-cell lymphoma (LBCL) is commonly ascribed to antigen loss or CAR-T exhaustion. Multiantigen targeting and programmed cell death protein-1 blockade are rational approaches to prevent relapse. Here, we test CD19/22 dual-targeting CAR-T (AUTO3) plus pembrolizumab in relapsed/refractory LBCL (NCT03289455). End points include toxicity (primary) and response rates (secondary). Fifty-two patients received AUTO3 and 48/52 received pembrolizumab. Median age was 59 years (range, 27-83), 46/52 had stage III/ IV disease and median follow-up was 21.6 months. AUTO3 was safe; grade 1-2 and grade 3 cytokine release syndrome affected 18/52 (34.6%) …


Safety, Tolerability, And Effectiveness Of The Sodium-Glucose Cotransporter 2 Inhibitor (Sglt2i) Dapagliflozin In Combination With Standard Chemotherapy For Patients With Advanced, Inoperable Pancreatic Adenocarcinoma: A Phase 1b Observational Study, Lauren K Park, Kian-Huat Lim, Jonas Volkman, Mina Abdiannia, Hannah Johnston, Zack Nigogosyan, Marilyn J Siegel, Janet B Mcgill, Alexis M Mckee, Maamoun Salam, Rong M Zhang, Da Ma, Karteek Popuri, Vincent Tze Yang Chow, Mirza Faisal Beg, William G Hawkins, Linda R Peterson, Joseph E Ippolito May 2023

Safety, Tolerability, And Effectiveness Of The Sodium-Glucose Cotransporter 2 Inhibitor (Sglt2i) Dapagliflozin In Combination With Standard Chemotherapy For Patients With Advanced, Inoperable Pancreatic Adenocarcinoma: A Phase 1b Observational Study, Lauren K Park, Kian-Huat Lim, Jonas Volkman, Mina Abdiannia, Hannah Johnston, Zack Nigogosyan, Marilyn J Siegel, Janet B Mcgill, Alexis M Mckee, Maamoun Salam, Rong M Zhang, Da Ma, Karteek Popuri, Vincent Tze Yang Chow, Mirza Faisal Beg, William G Hawkins, Linda R Peterson, Joseph E Ippolito

2020-Current year OA Pubs

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy. Thus, there is an urgent need for safe and effective novel therapies. PDAC's excessive reliance on glucose metabolism for its metabolic needs provides a target for metabolic therapy. Preclinical PDAC models have demonstrated that targeting the sodium-glucose co-transporter-2 (SGLT2) with dapagliflozin may be a novel strategy. Whether dapagliflozin is safe and efficacious in humans with PDAC is unclear.

METHODS: We performed a phase 1b observational study (ClinicalTrials.gov ID NCT04542291; registered 09/09/2020) to test the safety and tolerability of dapagliflozin (5 mg p.o./day × 2 weeks escalated to 10 mg p.o./day × …


The Evolution Of Primary Care Telehealth Disparities During Covid-19: Retrospective Cohort Study, Rachel D'Amico, Patrick M Schnell, Randi Foraker, J Nwando Olayiwola, Daniel E Jonas, Seuli Bose Brill May 2023

The Evolution Of Primary Care Telehealth Disparities During Covid-19: Retrospective Cohort Study, Rachel D'Amico, Patrick M Schnell, Randi Foraker, J Nwando Olayiwola, Daniel E Jonas, Seuli Bose Brill

2020-Current year OA Pubs

BACKGROUND: Telehealth has become widely used as a novel way to provide outpatient care during the COVID-19 pandemic, but data about telehealth use in primary care remain limited. Studies in other specialties raise concerns that telehealth may be widening existing health care disparities, requiring further scrutiny of trends in telehealth use.

OBJECTIVE: Our study aims to further characterize sociodemographic differences in primary care via telehealth compared to in-person office visits before and during the COVID-19 pandemic and determine if these disparities changed throughout 2020.

METHODS: We conducted a retrospective cohort study in a large US academic center with 46 primary …


Choroid Plexus-Targeted Nkcc1 Overexpression To Treat Post-Hemorrhagic Hydrocephalus, Cameron Sadegh, Yong Zhang, Michael J Holtzman, Et Al. May 2023

Choroid Plexus-Targeted Nkcc1 Overexpression To Treat Post-Hemorrhagic Hydrocephalus, Cameron Sadegh, Yong Zhang, Michael J Holtzman, Et Al.

2020-Current year OA Pubs

Post-hemorrhagic hydrocephalus (PHH) refers to a life-threatening accumulation of cerebrospinal fluid (CSF) that occurs following intraventricular hemorrhage (IVH). An incomplete understanding of this variably progressive condition has hampered the development of new therapies beyond serial neurosurgical interventions. Here, we show a key role for the bidirectional Na-K-Cl cotransporter, NKCC1, in the choroid plexus (ChP) to mitigate PHH. Mimicking IVH with intraventricular blood led to increased CSF [K


Distress Related To Psychotic Experiences: Enhancing The World Health Organization Composite International Diagnostic Interview Psychosis Screen, Hans Oh, Nicole R Karcher, Nirit Soffer-Dudek, Ai Koyanagi, Megan Besecker, Jordan E Devylder May 2023

Distress Related To Psychotic Experiences: Enhancing The World Health Organization Composite International Diagnostic Interview Psychosis Screen, Hans Oh, Nicole R Karcher, Nirit Soffer-Dudek, Ai Koyanagi, Megan Besecker, Jordan E Devylder

2020-Current year OA Pubs

BACKGROUND: The abbreviated version of the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI) psychosis screen tends to yield high prevalence in online samples. Psychotic Experiences (PE) may not necessarily indicate current or imminent psychopathology; however, distressing PE appear to be more clinically informative.

METHODS: We analyzed data collected from an online survey administered to a Qualtrics panel (N = 2522 adults). Using multivariable logistic regression, we examined the association between PE (with and without associated distress) and several mental health outcomes, adjusting for age, gender, and race/ethnicity.

RESULTS: Individuals with distressing PE had greater odds of most mental …


How Does Facilitation In Healthcare Work? Using Mechanism Mapping To Illuminate The Black Box Of A Meta-Implementation Strategy, Amy M Kilbourne, Elvin Geng, Ingrid Eshun-Wilson, Shannon Sweeney, Donna Shelley, Deborah J Cohen, Joann E Kirchner, Maria E Fernandez, Michael L Parchman May 2023

How Does Facilitation In Healthcare Work? Using Mechanism Mapping To Illuminate The Black Box Of A Meta-Implementation Strategy, Amy M Kilbourne, Elvin Geng, Ingrid Eshun-Wilson, Shannon Sweeney, Donna Shelley, Deborah J Cohen, Joann E Kirchner, Maria E Fernandez, Michael L Parchman

2020-Current year OA Pubs

BACKGROUND: Healthcare facilitation, an implementation strategy designed to improve the uptake of effective clinical innovations in routine practice, has produced promising yet mixed results in randomized implementation trials and has not been fully researched across different contexts.

OBJECTIVE: Using mechanism mapping, which applies directed acyclic graphs that decompose an effect of interest into hypothesized causal steps and mechanisms, we propose a more concrete description of how healthcare facilitation works to inform its further study as a meta-implementation strategy.

METHODS: Using a modified Delphi consensus process, co-authors developed the mechanistic map based on a three-step process. First, they developed an initial …


Genome-Wide Association Study Of Breast Density Among Women Of African Ancestry, Shefali Setia Verma, Lindsay Guare, Sarah Ehsan, Aimilia Gastounioti, Gabrielle Scales, Marylyn D Ritchie, Despina Kontos, Anne Marie Mccarthy, Penn Medicine Biobank May 2023

Genome-Wide Association Study Of Breast Density Among Women Of African Ancestry, Shefali Setia Verma, Lindsay Guare, Sarah Ehsan, Aimilia Gastounioti, Gabrielle Scales, Marylyn D Ritchie, Despina Kontos, Anne Marie Mccarthy, Penn Medicine Biobank

2020-Current year OA Pubs

Breast density, the amount of fibroglandular versus fatty tissue in the breast, is a strong breast cancer risk factor. Understanding genetic factors associated with breast density may help in clarifying mechanisms by which breast density increases cancer risk. To date, 50 genetic loci have been associated with breast density, however, these studies were performed among predominantly European ancestry populations. We utilized a cohort of women aged 40-85 years who underwent screening mammography and had genetic information available from the Penn Medicine BioBank to conduct a Genome-Wide Association Study (GWAS) of breast density among 1323 women of African ancestry. For each …


Circadian Clock Protein Bmal1 Broadly Influences Autophagy And Endolysosomal Function In Astrocytes, Celia A Mckee, Alexander J Polino, Melvin W King, Erik S Musiek May 2023

Circadian Clock Protein Bmal1 Broadly Influences Autophagy And Endolysosomal Function In Astrocytes, Celia A Mckee, Alexander J Polino, Melvin W King, Erik S Musiek

2020-Current year OA Pubs

An emerging role for the circadian clock in autophagy and lysosome function has opened new avenues for exploration in the field of neurodegeneration. The daily rhythms of circadian clock proteins may coordinate gene expression programs involved not only in daily rhythms but in many cellular processes. In the brain, astrocytes are critical for sensing and responding to extracellular cues to support neurons. The core clock protein BMAL1 serves as the primary positive circadian transcriptional regulator and its depletion in astrocytes not only disrupts circadian function but also leads to a unique cell-autonomous activation phenotype. We report here that astrocyte-specific deletion …


A Single-Cell Multiomic Analysis Of Kidney Organoid Differentiation, Yasuhiro Yoshimura, Yoshiharu Muto, Nicolas Ledru, Haojia Wu, Kohei Omachi, Jeffrey H Miner, Benjamin D Humphreys May 2023

A Single-Cell Multiomic Analysis Of Kidney Organoid Differentiation, Yasuhiro Yoshimura, Yoshiharu Muto, Nicolas Ledru, Haojia Wu, Kohei Omachi, Jeffrey H Miner, Benjamin D Humphreys

2020-Current year OA Pubs

Kidney organoids differentiated from pluripotent stem cells are powerful models of kidney development and disease but are characterized by cell immaturity and off-target cell fates. Comparing the cell-specific gene regulatory landscape during organoid differentiation with human adult kidney can serve to benchmark progress in differentiation at the epigenome and transcriptome level for individual organoid cell types. Using single-cell multiome and histone modification analysis, we report more broadly open chromatin in organoid cell types compared to the human adult kidney. We infer enhancer dynamics by cis-coaccessibility analysis and validate an enhancer driving transcription of


Modulating Fast Skeletal Muscle Contraction Protects Skeletal Muscle In Animal Models Of Duchenne Muscular Dystrophy, Alan J. Russell, Twlya I. Juehne, Jinsheng Yu, Et Al. May 2023

Modulating Fast Skeletal Muscle Contraction Protects Skeletal Muscle In Animal Models Of Duchenne Muscular Dystrophy, Alan J. Russell, Twlya I. Juehne, Jinsheng Yu, Et Al.

2020-Current year OA Pubs

Duchenne muscular dystrophy (DMD) is a lethal muscle disease caused by absence of the protein dystrophin, which acts as a structural link between the basal lamina and contractile machinery to stabilize muscle membranes in response to mechanical stress. In DMD, mechanical stress leads to exaggerated membrane injury and fiber breakdown, with fast fibers being the most susceptible to damage. A major contributor to this injury is muscle contraction, controlled by the motor protein myosin. However, how muscle contraction and fast muscle fiber damage contribute to the pathophysiology of DMD has not been well characterized. We explored the role of fast …


Safety And Efficacy Of Axicabtagene Ciloleucel Versus Standard Of Care In Patients 65 Years Of Age Or Older With Relapsed/Refractory Large B-Cell Lymphoma, Jason R Westin, Armin Ghobadi, Et Al. May 2023

Safety And Efficacy Of Axicabtagene Ciloleucel Versus Standard Of Care In Patients 65 Years Of Age Or Older With Relapsed/Refractory Large B-Cell Lymphoma, Jason R Westin, Armin Ghobadi, Et Al.

2020-Current year OA Pubs

PURPOSE: Older patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) may be considered ineligible for curative-intent therapy including high-dose chemotherapy with autologous stem-cell transplantation (HDT-ASCT). Here, we report outcomes of a preplanned subgroup analysis of patients ≥65 years in ZUMA-7.

PATIENTS AND METHODS: Patients with LBCL refractory to or relapsed ≤12 months after first-line chemoimmunotherapy were randomized 1:1 to axicabtagene ciloleucel [axi-cel; autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy] or standard of care (SOC; 2-3 cycles of chemoimmunotherapy followed by HDT-ASCT). The primary endpoint was event-free survival (EFS). Secondary endpoints included safety and patient-reported outcomes (PROs).

RESULTS: Fifty-one and …


Single-Nucleus Multi-Omics Of Human Stem Cell-Derived Islets Identifies Deficiencies In Lineage Specification, Punn Augsornworawat, Nathaniel J Hogrebe, Matthew Ishahak, Mason D Schmidt, Erica Marquez, Marlie M Maestas, Daniel A Veronese-Paniagua, Sarah E Gale, Julia R Miller, Leonardo Velazco-Cruz, Jeffrey R Millman May 2023

Single-Nucleus Multi-Omics Of Human Stem Cell-Derived Islets Identifies Deficiencies In Lineage Specification, Punn Augsornworawat, Nathaniel J Hogrebe, Matthew Ishahak, Mason D Schmidt, Erica Marquez, Marlie M Maestas, Daniel A Veronese-Paniagua, Sarah E Gale, Julia R Miller, Leonardo Velazco-Cruz, Jeffrey R Millman

2020-Current year OA Pubs

Insulin-producing β cells created from human pluripotent stem cells have potential as a therapy for insulin-dependent diabetes, but human pluripotent stem cell-derived islets (SC-islets) still differ from their in vivo counterparts. To better understand the state of cell types within SC-islets and identify lineage specification deficiencies, we used single-nucleus multi-omic sequencing to analyse chromatin accessibility and transcriptional profiles of SC-islets and primary human islets. Here we provide an analysis that enabled the derivation of gene lists and activity for identifying each SC-islet cell type compared with primary islets. Within SC-islets, we found that the difference between β cells and awry …


Strategies To Bridge Equitable Implementation Of Telehealth, Allison M Gustavson, Allison A Lewinski, Ellen E Fitzsimmons-Craft, Gloria D Coronado, Sarah E Linke, Denalee M O'Malley, Alyce S Adams, Russell E Glasgow, Lisa M Klesges May 2023

Strategies To Bridge Equitable Implementation Of Telehealth, Allison M Gustavson, Allison A Lewinski, Ellen E Fitzsimmons-Craft, Gloria D Coronado, Sarah E Linke, Denalee M O'Malley, Alyce S Adams, Russell E Glasgow, Lisa M Klesges

2020-Current year OA Pubs

During the COVID-19 pandemic, the rapid scaling of telehealth limited the extent to which proactive planning for equitable implementation was possible. The deployment of telehealth will persist in the postpandemic era, given patient preferences, advances in technologies, growing acceptance of telehealth, and the potential to overcome barriers to serve populations with limited access to high-quality in-person care. However, aspects and unintended consequences of telehealth may leave some groups underserved or unserved, and corrective implementation plans that address equitable access will be needed. The purposes of this paper are to (1) describe equitable implementation in telehealth and (2) integrate an equity …


Biomechanical Models And Mechanisms Of Cellular Morphogenesis And Cerebral Cortical Expansion And Folding, David C Van Essen May 2023

Biomechanical Models And Mechanisms Of Cellular Morphogenesis And Cerebral Cortical Expansion And Folding, David C Van Essen

2020-Current year OA Pubs

Morphogenesis of the nervous system involves a highly complex spatio-temporal pattern of physical forces (mainly tension and pressure) acting on cells and tissues that are pliable but have an intricately organized cytoskeletal infrastructure. This review begins by covering basic principles of biomechanics and the core cytoskeletal toolkit used to regulate the shapes of cells and tissues during embryogenesis and neural development. It illustrates how the principle of 'tensegrity' provides a useful conceptual framework for understanding how cells dynamically respond to forces that are generated internally or applied externally. The latter part of the review builds on this foundation in considering …


Cortical Atrophy And Leukoaraiosis, Imaging Markers Of Cerebrovascular Small Vessel Disease, Are Associated With Driving Behavior Changes Among Cognitively Normal Older Adults, Ganesh M Babulal, Ling Chen, David B Carr, Ann M Johnson, Joshua S Shimony, Jason Doherty, Samantha Murphy, Alexis Walker, Hailee Domash, Russ Hornbeck, Sarah Keefe, Shaney Flores, Cyrus A Raji, John C Morris, Beau M Ances, Tammie L S Benzinger May 2023

Cortical Atrophy And Leukoaraiosis, Imaging Markers Of Cerebrovascular Small Vessel Disease, Are Associated With Driving Behavior Changes Among Cognitively Normal Older Adults, Ganesh M Babulal, Ling Chen, David B Carr, Ann M Johnson, Joshua S Shimony, Jason Doherty, Samantha Murphy, Alexis Walker, Hailee Domash, Russ Hornbeck, Sarah Keefe, Shaney Flores, Cyrus A Raji, John C Morris, Beau M Ances, Tammie L S Benzinger

2020-Current year OA Pubs

BACKGROUND: Cerebral small vessel disease (CSVD) as measured by cortical atrophy and white matter hyperintensities [leukoaraiosis], captured via magnetic resonance imaging (MRI) are increasing in prevalence due to the growth of the aging population and an increase in cardiovascular risk factors in the population. CSVD impacts cognitive function and mobility, but it is unclear if it affects complex, functional activities like driving.

METHODS: In a cohort of 163 cognitively normal, community-dwelling older adults (age ≥ 65), we compared naturalistic driving behavior with mild/moderate leukoaraiosis, cortical atrophy, or their combined rating in a clinical composite termed, aging-related changes to those without …


Role Of Midkine In Cancer Drug Resistance: Regulators Of Its Expression And Its Molecular Targeting, Minakshi Saikia, Nathan Cheung, Abhay Kumar Singh, Vaishali Kapoor May 2023

Role Of Midkine In Cancer Drug Resistance: Regulators Of Its Expression And Its Molecular Targeting, Minakshi Saikia, Nathan Cheung, Abhay Kumar Singh, Vaishali Kapoor

2020-Current year OA Pubs

Molecules involved in drug resistance can be targeted for better therapeutic efficacies. Research on midkine (MDK) has escalated in the last few decades, which affirms a positive correlation between disease progression and MDK expression in most cancers and indicates its association with multi-drug resistance in cancer. MDK, a secretory cytokine found in blood, can be exploited as a potent biomarker for the non-invasive detection of drug resistance expressed in various cancers and, thereby, can be targeted. We summarize the current information on the involvement of MDK in drug resistance, and transcriptional regulators of its expression and highlight its potential as …


A Phase 1b Randomized Clinical Trial Of Ct1812 To Measure Aβ Oligomer Displacement In Alzheimer's Disease Using An Indwelling Csf Catheter, Kelsie M Labarbera, Carla M Yuede, Hannah M Edwards, Woodrow D Gardiner, John R Cirrito, Et Al. May 2023

A Phase 1b Randomized Clinical Trial Of Ct1812 To Measure Aβ Oligomer Displacement In Alzheimer's Disease Using An Indwelling Csf Catheter, Kelsie M Labarbera, Carla M Yuede, Hannah M Edwards, Woodrow D Gardiner, John R Cirrito, Et Al.

2020-Current year OA Pubs

No abstract provided.


Trem2 Inhibition Triggers Antitumor Cell Activity Of Myeloid Cells In Glioblastoma, Rui Sun, Rowland Han, Colin Mccornack, Saad Khan, G Travis Tabor, Yun Chen, Jinchao Hou, Haowu Jiang, Kathleen M Schoch, Diane D Mao, Ryan Cleary, Alicia Yang, Qin Liu, Jingqin Luo, Allegra Petti, Timothy M Miller, Jason D Ulrich, David M Holtzman, Albert H Kim May 2023

Trem2 Inhibition Triggers Antitumor Cell Activity Of Myeloid Cells In Glioblastoma, Rui Sun, Rowland Han, Colin Mccornack, Saad Khan, G Travis Tabor, Yun Chen, Jinchao Hou, Haowu Jiang, Kathleen M Schoch, Diane D Mao, Ryan Cleary, Alicia Yang, Qin Liu, Jingqin Luo, Allegra Petti, Timothy M Miller, Jason D Ulrich, David M Holtzman, Albert H Kim

2020-Current year OA Pubs

Triggering receptor expressed on myeloid cells 2 (TREM2) plays important roles in brain microglial function in neurodegenerative diseases, but the role of TREM2 in the GBM TME has not been examined. Here, we found that TREM2 is highly expressed in myeloid subsets, including macrophages and microglia in human and mouse GBM tumors and that high TREM2 expression correlates with poor prognosis in patients with GBM. TREM2 loss of function in human macrophages and mouse myeloid cells increased interferon-γ-induced immunoactivation, proinflammatory polarization, and tumoricidal capacity. In orthotopic mouse GBM models, mice with chronic and acute Trem2 loss of function exhibited decreased …


Effects Of A Virtual Voice-Based Coach Delivering Problem-Solving Treatment On Emotional Distress And Brain Function: A Pilot Rct In Depression And Anxiety, Thomas Kannampallil, Et Al. May 2023

Effects Of A Virtual Voice-Based Coach Delivering Problem-Solving Treatment On Emotional Distress And Brain Function: A Pilot Rct In Depression And Anxiety, Thomas Kannampallil, Et Al.

2020-Current year OA Pubs

Consumer-based voice assistants have the ability to deliver evidence-based treatment, but their therapeutic potential is largely unknown. In a pilot trial of a virtual voice-based coach, Lumen, delivering problem-solving treatment, adults with mild-to-moderate depression and/or anxiety were randomized to the Lumen intervention (n = 42) or waitlist control (n = 21). The main outcomes included changes in neural measures of emotional reactivity and cognitive control, and Hospital Anxiety and Depression Scale [HADS] symptom scores over 16 weeks. Participants were 37.8 years (SD = 12.4), 68% women, 25% Black, 24% Latino, and 11% Asian. Activation of the right dlPFC (neural region …


Five-Year Follow-Up Of Zuma-1 Supports The Curative Potential Of Axicabtagene Ciloleucel In Refractory Large B-Cell Lymphoma, Sattva S Neelapu, Armin Ghobadi, Nancy L Bartlett, Et Al. May 2023

Five-Year Follow-Up Of Zuma-1 Supports The Curative Potential Of Axicabtagene Ciloleucel In Refractory Large B-Cell Lymphoma, Sattva S Neelapu, Armin Ghobadi, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

In phase 2 of ZUMA-1, a single-arm, multicenter, registrational trial, axicabtagene ciloleucel (axi-cel) autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy demonstrated durable responses at 2 years in patients with refractory large B-cell lymphoma (LBCL). Here, we assessed outcomes in ZUMA-1 after 5 years of follow-up. Eligible adults received lymphodepleting chemotherapy followed by axi-cel (2 × 106 cells per kg). Investigator-assessed response, survival, safety, and pharmacokinetics were assessed in patients who had received treatment. The objective response rate in these 101 patients was 83% (58% complete response rate); with a median follow-up of 63.1 months, responses were ongoing in 31% …


Data Envelopment Analysis To Evaluate The Efficiency Of Tobacco Treatment Programs In The Nci Moonshot Cancer Center Cessation Initiative, Kathryn Pluta, Li-Shiun Chen, Et Al. May 2023

Data Envelopment Analysis To Evaluate The Efficiency Of Tobacco Treatment Programs In The Nci Moonshot Cancer Center Cessation Initiative, Kathryn Pluta, Li-Shiun Chen, Et Al.

2020-Current year OA Pubs

BACKGROUND: The Cancer Center Cessation Initiative (C3I) is a National Cancer Institute (NCI) Cancer Moonshot Program that supports NCI-designated cancer centers developing tobacco treatment programs for oncology patients who smoke. C3I-funded centers implement evidence-based programs that offer various smoking cessation treatment components (e.g., counseling, Quitline referrals, access to medications). While evaluation of implementation outcomes in C3I is guided by evaluation of reach and effectiveness (via RE-AIM), little is known about technical efficiency-i.e., how inputs (e.g., program costs, staff time) influence implementation outcomes (e.g., reach, effectiveness). This study demonstrates the application of data envelopment analysis (DEA) as an implementation science tool …


Co-Clinical Imaging Metadata Information (Cimi) For Cancer Research To Promote Open Science, Standardization, And Reproducibility In Preclinical Imaging, Stephen M Moore, James D Quirk, Andrew W Lassiter, Richard Laforest, Kooresh I Shoghi, Et Al. May 2023

Co-Clinical Imaging Metadata Information (Cimi) For Cancer Research To Promote Open Science, Standardization, And Reproducibility In Preclinical Imaging, Stephen M Moore, James D Quirk, Andrew W Lassiter, Richard Laforest, Kooresh I Shoghi, Et Al.

2020-Current year OA Pubs

Preclinical imaging is a critical component in translational research with significant complexities in workflow and site differences in deployment. Importantly, the National Cancer Institute's (NCI) precision medicine initiative emphasizes the use of translational co-clinical oncology models to address the biological and molecular bases of cancer prevention and treatment. The use of oncology models, such as patient-derived tumor xenografts (PDX) and genetically engineered mouse models (GEMMs), has ushered in an era of co-clinical trials by which preclinical studies can inform clinical trials and protocols, thus bridging the translational divide in cancer research. Similarly, preclinical imaging fills a translational gap as an …


Protocol For A Scoping Review Of Health Equity Frameworks And Models Applied In Empirical Studies Of Chronic Disease Prevention And Control, Callie Walsh-Bailey, Amanda Gilbert, Thembekile Shato, Brittney Sandler, Ana A Baumann, Cory D Bradley, Gabriella M Mcloughlin, F Hunter Mcguire, Meredith P Fort, Rachel G Tabak May 2023

Protocol For A Scoping Review Of Health Equity Frameworks And Models Applied In Empirical Studies Of Chronic Disease Prevention And Control, Callie Walsh-Bailey, Amanda Gilbert, Thembekile Shato, Brittney Sandler, Ana A Baumann, Cory D Bradley, Gabriella M Mcloughlin, F Hunter Mcguire, Meredith P Fort, Rachel G Tabak

2020-Current year OA Pubs

BACKGROUND: Chronic diseases, such as cancers and cardiovascular diseases, present the greatest burden of morbidity and mortality worldwide. This burden disproportionately affects historically marginalized populations. Health equity is rapidly gaining increased attention in public health, health services, and implementation research, though many health inequities persist. Health equity frameworks and models (FM) have been called upon to guide equity-focused chronic disease and implementation research. However, there is no clear synthesis of the health equity FM used in chronic disease research or how these are applied in empirical studies. This scoping review seeks to fill this gap by identifying and characterizing health …


Two Forms Of Asynchronous Release With Distinctive Spatiotemporal Dynamics In Central Synapses, Gerardo Malagon, Jongyun Myeong, Vitaly A Klyachko May 2023

Two Forms Of Asynchronous Release With Distinctive Spatiotemporal Dynamics In Central Synapses, Gerardo Malagon, Jongyun Myeong, Vitaly A Klyachko

2020-Current year OA Pubs

Asynchronous release is a ubiquitous form of neurotransmitter release that persists for tens to hundreds of milliseconds after an action potential. How asynchronous release is organized and regulated at the synaptic active zone (AZ) remains debatable. Using nanoscale-precision imaging of individual release events in rat hippocampal synapses, we observed two spatially distinct subpopulations of asynchronous events, ~75% of which occurred inside the AZ and with a bias towards the AZ center, while ~25% occurred outside of the functionally defined AZ, that is, ectopically. The two asynchronous event subpopulations also differed from each other in temporal properties, with ectopic events occurring …


Study Design And Protocol Of A Stepped Wedge Cluster Randomized Trial Using A Practical Implementation Strategy As A Model For Hypertension-Hiv Integration - The Map-It Trial, Angela A Aifah, Daphne Lew, Et Al. May 2023

Study Design And Protocol Of A Stepped Wedge Cluster Randomized Trial Using A Practical Implementation Strategy As A Model For Hypertension-Hiv Integration - The Map-It Trial, Angela A Aifah, Daphne Lew, Et Al.

2020-Current year OA Pubs

BACKGROUND: As people living with HIV (PLWH) experience earlier and more pronounced onset of noncommunicable diseases (NCDs), advancing integrated care networks and models in low-resource-high-need settings is critical. Leveraging current health system initiatives and addressing gaps in treatment for PLWH, we report our approach using a late-stage (T4) implementation research study to test the adoption and sustainability of a proven-effective implementation strategy which has been minimally applied in low-resource settings for the integration of hypertension control into HIV treatment. We detail our protocol for the Managing Hypertension Among People Living with HIV: an Integrated Model (MAP-IT) trial, which uses a …


Diagnosis And Treatment Of Fungal Infections In Lung Transplant Recipients, Jesus E Escamilla, Spenser E January, Rodrigo Vazquez Guillamet May 2023

Diagnosis And Treatment Of Fungal Infections In Lung Transplant Recipients, Jesus E Escamilla, Spenser E January, Rodrigo Vazquez Guillamet

2020-Current year OA Pubs

Fungal infections are a significant source of morbidity in the lung transplant population via direct allograft damage and predisposing patients to the development of chronic lung allograft dysfunction. Prompt diagnosis and treatment are imperative to limit allograft damage. This review article discusses incidence, risk factors, and symptoms with a specific focus on diagnostic and treatment strategies in the lung transplant population for fungal infections caused by


Dynamic Frailty Risk Assessment Among Older Adults With Multiple Myeloma: A Population-Based Cohort Study, Hira Mian, Tanya M Wildes, Ravi Vij, Matthew J Pianko, Ajay Major, Mark A Fiala May 2023

Dynamic Frailty Risk Assessment Among Older Adults With Multiple Myeloma: A Population-Based Cohort Study, Hira Mian, Tanya M Wildes, Ravi Vij, Matthew J Pianko, Ajay Major, Mark A Fiala

2020-Current year OA Pubs

Multiple myeloma (MM) is a cancer of older adults and those who are more frail are at high risk of poor outcomes. Current tools for identifying and categorizing frail patients are often static and measured only at the time of diagnosis. The concept of dynamic frailty (i.e. frailty changing over time) is largely unexplored in MM. In our study, adults with newly-diagnosed MM who received novel drugs between the years 2007-2014 were identified in the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked databases. Using a previously published cumulative deficit approach, a frailty index score was calculated at diagnosis and each …


Bronchoscopic Evaluation Of A Steerable Needle For Simulated Tumor Targets In The Lung Periphery: A Feasibility Study (Bullseye), Alexander C. Chen, Michael Machuzak, George Cheng, Momen M. Wahidi May 2023

Bronchoscopic Evaluation Of A Steerable Needle For Simulated Tumor Targets In The Lung Periphery: A Feasibility Study (Bullseye), Alexander C. Chen, Michael Machuzak, George Cheng, Momen M. Wahidi

2020-Current year OA Pubs

BACKGROUND: Peripheral bronchoscopy is often performed to biopsy peripheral pulmonary lesions. Despite technological advancements to improve reach and access to the lung periphery, the diagnostic yield of peripheral bronchoscopy has been inconsistent, and challenging, particularly for lesions that are adjacent to peripheral bronchi. Current biopsy instruments are reliant on the catheter or scope to align properly with targeted lesions.

OBJECTIVES: This study evaluates the feasibility of using a steerable biopsy needle to gain access to peripheral tumor targets in a cadaveric model.

METHODS: Simulated tumor targets 10-30 mm in axial diameter were placed into human cadavers. Bronchoscopy was performed using …


Layperson Perception Of Reflux-Related Symptoms, Jakob L. Fischer, Anthony M. Tolisano, Alvaro I. Navarro, Lily Trinh, Waleed M. Abuzeid, Ian M. Humphreys, Nadeem A. Akbar, Sharan Shah, John S. Schneider, Charles A. Riley, Edward D. Mccoul May 2023

Layperson Perception Of Reflux-Related Symptoms, Jakob L. Fischer, Anthony M. Tolisano, Alvaro I. Navarro, Lily Trinh, Waleed M. Abuzeid, Ian M. Humphreys, Nadeem A. Akbar, Sharan Shah, John S. Schneider, Charles A. Riley, Edward D. Mccoul

2020-Current year OA Pubs

OBJECTIVE: To assess for differences of intended meaning in the description of reflux-related symptoms among otolaryngology patients and clinicians.

STUDY DESIGN: Cross-sectional survey-based study.

SETTING: Five tertiary, academic otolaryngology practices.

METHODS: Between June 2020 and July 2022, a questionnaire consisting of 20 common descriptors of reflux-related symptoms within four domains (throat-, chest-, stomach-, and sensory-related symptoms) was completed by patients. Attending otolaryngologists at five academic medical centers then completed the same survey. The primary outcome was to assess differences in patient and clinician perceptions of reflux-related symptoms. Differences based on geographic location was a secondary outcome.

RESULTS: A total of …


T Helper 2 Cells Control Monocyte To Tissue-Resident Macrophage Differentiation During Nematode Infection Of The Pleural Cavity, Conor M. Finlay, Gwendalyn J. Randolph, Et Al. May 2023

T Helper 2 Cells Control Monocyte To Tissue-Resident Macrophage Differentiation During Nematode Infection Of The Pleural Cavity, Conor M. Finlay, Gwendalyn J. Randolph, Et Al.

2020-Current year OA Pubs

No abstract provided.