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Full-Text Articles in Medicine and Health Sciences

Protocol To Isolate Rbp-Mrna Complexes Using Rna-Clip And Examine Target Mrnas, Valerie Blanc, Elizabeth A Molitor, Nicholas O Davidson May 2023

Protocol To Isolate Rbp-Mrna Complexes Using Rna-Clip And Examine Target Mrnas, Valerie Blanc, Elizabeth A Molitor, Nicholas O Davidson

2020-Current year OA Pubs

RNA-binding proteins (RBPs) regulate diverse functions by interacting with target transcripts. Here we present a protocol to isolate RBP-mRNA complexes using RNA-CLIP and examine target mRNAs in association with ribosomal populations. We describe steps to identify specific RBPs and RNA targets reflecting a variety of developmental, physiological, and pathological states. This protocol enables RNP complex isolation from tissue sources (liver and small intestine) or populations of primary cells (hepatocytes), but not at a single-cell level. For complete details on the use and execution of this protocol, please refer to Blanc et al. (2014)


Smoking Status, Nicotine Medication, Vaccination, And Covid-19 Hospital Outcomes: Findings From The Covid Ehr Cohort At The University Of Wisconsin (Cec-Uw) Study, Thomas M Piasecki, Li-Shiun Chen, Et Al. May 2023

Smoking Status, Nicotine Medication, Vaccination, And Covid-19 Hospital Outcomes: Findings From The Covid Ehr Cohort At The University Of Wisconsin (Cec-Uw) Study, Thomas M Piasecki, Li-Shiun Chen, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Available evidence is mixed concerning associations between smoking status and COVID-19 clinical outcomes. Effects of nicotine replacement therapy (NRT) and vaccination status on COVID-19 outcomes in smokers are unknown.

METHODS: Electronic health record data from 104 590 COVID-19 patients hospitalized February 1, 2020 to September 30, 2021 in 21 U.S. health systems were analyzed to assess associations of smoking status, in-hospital NRT prescription, and vaccination status with in-hospital death and ICU admission.

RESULTS: Current (n = 7764) and never smokers (n = 57 454) did not differ on outcomes after adjustment for age, sex, race, ethnicity, insurance, body mass …


Integrating Tobacco Treatment Into Oncology Care: Reach And Effectiveness Of Evidence-Based Tobacco Treatment Across National Cancer Institute-Designated Cancer Centers, Sarah D Hohl, Alex T Ramsey, Li-Shiun Chen, Et Al. May 2023

Integrating Tobacco Treatment Into Oncology Care: Reach And Effectiveness Of Evidence-Based Tobacco Treatment Across National Cancer Institute-Designated Cancer Centers, Sarah D Hohl, Alex T Ramsey, Li-Shiun Chen, Et Al.

2020-Current year OA Pubs

PURPOSE: Quitting smoking improves patients' clinical outcomes, yet smoking is not commonly addressed as part of cancer care. The Cancer Center Cessation Initiative (C3I) supports National Cancer Institute-designated cancer centers to integrate tobacco treatment programs (TTPs) into routine cancer care. C3I centers vary in size, implementation strategies used, and treatment approaches. We examined associations of these contextual factors with treatment reach and smoking cessation effectiveness.

METHODS: This cross-sectional study used survey data from 28 C3I centers that reported tobacco treatment data during the first 6 months of 2021. Primary outcomes of interest were treatment reach (reach)-the proportion of patients identified …


Conditional Deletion Of Lrrc8a In The Brain Reduces Stroke Damage Independently Of Swelling-Activated Glutamate Release, Mustafa Balkaya, Preeti Dohare, Sophie Chen, Alexandra L Schober, Antonio M Fidaleo, Julia W Nalwalk, Rajan Sah, Alexander A Mongin May 2023

Conditional Deletion Of Lrrc8a In The Brain Reduces Stroke Damage Independently Of Swelling-Activated Glutamate Release, Mustafa Balkaya, Preeti Dohare, Sophie Chen, Alexandra L Schober, Antonio M Fidaleo, Julia W Nalwalk, Rajan Sah, Alexander A Mongin

2020-Current year OA Pubs

The ubiquitous volume-regulated anion channels (VRACs) facilitate cell volume control and contribute to many other physiological processes. Treatment with non-specific VRAC blockers or brain-specific deletion of the essential VRAC subunit LRRC8A is highly protective in rodent models of stroke. Here, we tested the widely accepted idea that the harmful effects of VRACs are mediated by release of the excitatory neurotransmitter glutamate. We produced conditional LRRC8A knockout either exclusively in astrocytes or in the majority of brain cells. Genetically modified mice were subjected to an experimental stroke (middle cerebral artery occlusion). The astrocytic LRRC8A knockout yielded no protection. Conversely, the brain-wide …


Using Mass Spectrometry Imaging To Map Fluxes Quantitatively In The Tumor Ecosystem, Michaela Schwaiger-Haber, Ethan Stancliffe, Dhanalakshmi S Anbukumar, Blake Sells, Jia Yi, Kevin Cho, Kayla Adkins-Travis, Milan G Chheda, Leah P Shriver, Gary J Patti May 2023

Using Mass Spectrometry Imaging To Map Fluxes Quantitatively In The Tumor Ecosystem, Michaela Schwaiger-Haber, Ethan Stancliffe, Dhanalakshmi S Anbukumar, Blake Sells, Jia Yi, Kevin Cho, Kayla Adkins-Travis, Milan G Chheda, Leah P Shriver, Gary J Patti

2020-Current year OA Pubs

Tumors are comprised of a multitude of cell types spanning different microenvironments. Mass spectrometry imaging (MSI) has the potential to identify metabolic patterns within the tumor ecosystem and surrounding tissues, but conventional workflows have not yet fully integrated the breadth of experimental techniques in metabolomics. Here, we combine MSI, stable isotope labeling, and a spatial variant of Isotopologue Spectral Analysis to map distributions of metabolite abundances, nutrient contributions, and metabolic turnover fluxes across the brains of mice harboring GL261 glioma, a widely used model for glioblastoma. When integrated with MSI, the combination of ion mobility, desorption electrospray ionization, and matrix …


Multi-Stakeholder Perspectives Regarding Preferred Modalities For Mental Health Intervention Delivered In The Orthopedic Clinic: A Qualitative Analysis, Abby L Cheng, Ashwin J Leo, Ryan P Calfee, Christopher J Dy, Melissa A Armbrecht, Joanna Abraham May 2023

Multi-Stakeholder Perspectives Regarding Preferred Modalities For Mental Health Intervention Delivered In The Orthopedic Clinic: A Qualitative Analysis, Abby L Cheng, Ashwin J Leo, Ryan P Calfee, Christopher J Dy, Melissa A Armbrecht, Joanna Abraham

2020-Current year OA Pubs

BACKGROUND: Although depressive and anxious symptoms negatively impact musculoskeletal health and orthopedic outcomes, a gap remains in identifying modalities through which mental health intervention can realistically be delivered during orthopedic care. The purpose of this study was to understand orthopedic stakeholders' perceptions regarding the feasibility, acceptability, and usability of digital, printed, and in-person intervention modalities to address mental health as part of orthopedic care.

METHODS: This single-center, qualitative study was conducted within a tertiary care orthopedic department. Semi-structured interviews were conducted between January and May 2022. Two stakeholder groups were interviewed using a purposive sampling approach until thematic saturation was …


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 × …


Predicting Alcohol-Related Memory Problems In Older Adults: A Machine Learning Study With Multi-Domain Features, Chella Kamarajan, Andrey P Anokhin, Sarah Hartz, Laura J Bierut, Vivia V Mccutcheon, Kathleen K Bucholz, Et Al. May 2023

Predicting Alcohol-Related Memory Problems In Older Adults: A Machine Learning Study With Multi-Domain Features, Chella Kamarajan, Andrey P Anokhin, Sarah Hartz, Laura J Bierut, Vivia V Mccutcheon, Kathleen K Bucholz, Et Al.

2020-Current year OA Pubs

Memory problems are common among older adults with a history of alcohol use disorder (AUD). Employing a machine learning framework, the current study investigates the use of multi-domain features to classify individuals with and without alcohol-induced memory problems. A group of 94 individuals (ages 50-81 years) with alcohol-induced memory problems (the memory group) were compared with a matched control group who did not have memory problems. The random forests model identified specific features from each domain that contributed to the classification of the memory group vs. the control group (AUC = 88.29%). Specifically, individuals from the memory group manifested a …


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


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 …


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 …


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 …


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 …


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 …


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


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 …


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 …


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 …


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 …


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 …


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 …


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 …


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.


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 …


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 …


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 …


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


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 …