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Adipocyte Lipin 1 Expression Associates With Human Metabolic Health And Regulates Systemic Metabolism In Mice, Andrew Lapoint, Jason M. Singer, Daniel Ferguson, Trevor M. Shew, M. Katie Renkemeyer, Hector H. Palacios, Rachael L. Field, Gordon I. Smith, Mai He, Gary J Patti, Samuel Klein, Jonathan R. Brestoff, Brian N. Finck, Et Al. Oct 2024

Adipocyte Lipin 1 Expression Associates With Human Metabolic Health And Regulates Systemic Metabolism In Mice, Andrew Lapoint, Jason M. Singer, Daniel Ferguson, Trevor M. Shew, M. Katie Renkemeyer, Hector H. Palacios, Rachael L. Field, Gordon I. Smith, Mai He, Gary J Patti, Samuel Klein, Jonathan R. Brestoff, Brian N. Finck, Et Al.

2020-Current year OA Pubs

Dysfunctional adipose tissue is believed to promote the development of hepatic steatosis and systemic insulin resistance, but many of the mechanisms involved are still unclear. Lipin 1 catalyzes the conversion of phosphatidic acid to diacylglycerol, the penultimate step of triglyceride synthesis, which is essential for lipid storage. Herein we found that adipose tissue LPIN1 expression is decreased in people with obesity compared with lean subjects, and low LPIN1 expression correlated with multi-tissue insulin resistance and increased rates of hepatic de novo lipogenesis. Comprehensive metabolic and multiomic phenotyping demonstrated that adipocyte-specific Lpin1-/- mice had a metabolically unhealthy phenotype, including liver and …


Immuno-Scanning Electron Microscopy Of Islet Primary Cilia, Sanja Sviben, Alexander J Polino, Isabella L Melena, Jing W Hughes Oct 2024

Immuno-Scanning Electron Microscopy Of Islet Primary Cilia, Sanja Sviben, Alexander J Polino, Isabella L Melena, Jing W Hughes

2020-Current year OA Pubs

The definitive demonstration of protein localization on primary cilia has been a challenge for cilia biologists. Primary cilia are solitary thread-like projections that have a specialized protein composition, but as the ciliary structure overlays the cell membrane and other cell parts, the identity of ciliary proteins are difficult to ascertain by conventional imaging approaches like immunofluorescence microscopy. Surface scanning electron microscopy combined with immunolabeling (immuno-SEM) bypasses some of these indeterminacies by unambiguously showing protein expression in the context of the three-dimensional ultrastructure of the cilium. Here, we apply immuno-SEM to specifically identify proteins on the primary cilia of mouse and …


Integrating Hypertension Detection And Management In Hiv Care In South Africa: Protocol For A Stepped-Wedged Cluster Randomized Effectiveness-Implementation Hybrid Trial, Karla I Galaviz, Charles W Goss, Aaloke Mody, Et Al. Oct 2024

Integrating Hypertension Detection And Management In Hiv Care In South Africa: Protocol For A Stepped-Wedged Cluster Randomized Effectiveness-Implementation Hybrid Trial, Karla I Galaviz, Charles W Goss, Aaloke Mody, Et Al.

2020-Current year OA Pubs

BACKGROUND: HIV clinical guidelines recommend hypertension detection and management to lower cardiovascular disease risk, but these have not been effectively implemented for people living with HIV (PWH). Addressing this implementation gap requires community-engaged implementation studies focused on addressing implementation barriers specific to the HIV care context.

METHODS: This protocol describes a type 2 effectiveness-implementation hybrid study conducted in nine primary care clinics in Johannesburg. The study will evaluate the effect of implementation strategies on guideline-recommended blood pressure assessment and management in HIV clinics and the effects of assessment/management on patient blood pressure. A stepped-wedge, cluster randomized study design was used …


A Proteomics Approach To Study Mouse Long Bones: Examining Baseline Differences And Mechanical Loading-Induced Bone Formation In Young-Adult And Old Mice, Christopher J Chermside-Scabbo, John T Shuster, Petra Erdmann-Gilmore, Eric Tycksen, Qiang Zhang, R Reid Townsend, Matthew J Silva Oct 2024

A Proteomics Approach To Study Mouse Long Bones: Examining Baseline Differences And Mechanical Loading-Induced Bone Formation In Young-Adult And Old Mice, Christopher J Chermside-Scabbo, John T Shuster, Petra Erdmann-Gilmore, Eric Tycksen, Qiang Zhang, R Reid Townsend, Matthew J Silva

2020-Current year OA Pubs

With aging, bone mass declines and the anabolic effects of skeletal loading diminish. While much research has focused on gene transcription, how bone ages and loses its mechanoresponsiveness at the protein level remains unclear. We developed a novel proteomics approach and performed a paired mass spectrometry and RNA-seq analysis on tibias from young-adult (5-month) and old (22-month) mice. We report the first correlation estimate between the bone proteome and transcriptome (Spearman


Thrombotic, Cardiovascular, And Microvascular Complications Of Myeloproliferative Neoplasms And Clonal Hematopoiesis (Chip): A Narrative Review, Andrew I Schafer, Douglas L Mann Oct 2024

Thrombotic, Cardiovascular, And Microvascular Complications Of Myeloproliferative Neoplasms And Clonal Hematopoiesis (Chip): A Narrative Review, Andrew I Schafer, Douglas L Mann

2020-Current year OA Pubs

The most common causes of morbidity and mortality in the myeloproliferative neoplasms (MPNs), with the exception of myelofibrosis, are venous and arterial thrombosis, as well as more recently discovered cardiovascular disease (CVD). Clonal hematopoiesis of indeterminate potential (CHIP) is the subclinical finding in an individual of somatic mutations that are also found in clinically overt MPNs and other myeloid malignancies. The prevalence of "silent" CHIP increases with age. CHIP can transform into a clinically overt MPN at an estimated rate of 0.5 to 1% per year. It is likely, therefore, but not proven, that many, if not all, MPN patients …


Fluid Biomarkers In The Context Of Amyloid-Targeting Disease-Modifying Treatments In Alzheimer's Disease, Yan Hu, Min Cho, Pallavi Sachdev, Jeffrey Dage, Suzanne Hendrix, Oskar Hansson, Randall J Bateman, Harald Hampel Oct 2024

Fluid Biomarkers In The Context Of Amyloid-Targeting Disease-Modifying Treatments In Alzheimer's Disease, Yan Hu, Min Cho, Pallavi Sachdev, Jeffrey Dage, Suzanne Hendrix, Oskar Hansson, Randall J Bateman, Harald Hampel

2020-Current year OA Pubs

Clinical management and therapeutics development for Alzheimer's disease (AD) have entered a new era, with recent approvals of monoclonal antibody therapies targeting the underlying pathophysiology of the disease and modifying its trajectory. Imaging and fluid biomarkers are becoming increasingly important in the clinical development of AD therapeutics. This review focuses on the evidence of fluid biomarkers from recent amyloid-β-targeting clinical trials, summarizing biomarker data across 12 trials. It further proposes a simple framework to put biomarker guidance in the context of amyloid-pathway-targeted disease modification, delineates factors that impact biomarker data in clinical trials, and highlights knowledge gaps and future directions. …


Systematic Perturbations Of Setd2, Nsd1, Nsd2, Nsd3, And Ash1l Reveal Their Distinct Contributions To H3k36 Methylation, Gerry A Shipman, Reinnier Padilla, Cynthia Horth, Bo Hu, Eric Bareke, Francisca N Vitorino, Joanna M Gongora, Benjamin A Garcia, Chao Lu, Jacek Majewski Oct 2024

Systematic Perturbations Of Setd2, Nsd1, Nsd2, Nsd3, And Ash1l Reveal Their Distinct Contributions To H3k36 Methylation, Gerry A Shipman, Reinnier Padilla, Cynthia Horth, Bo Hu, Eric Bareke, Francisca N Vitorino, Joanna M Gongora, Benjamin A Garcia, Chao Lu, Jacek Majewski

2020-Current year OA Pubs

BACKGROUND: Methylation of histone 3 lysine 36 (H3K36me) has emerged as an essential epigenetic component for the faithful regulation of gene expression. Despite its importance in development and disease, how the molecular agents collectively shape the H3K36me landscape is unclear.

RESULTS: We use mouse mesenchymal stem cells to perturb the H3K36me methyltransferases (K36MTs) and infer the activities of the five most prominent enzymes: SETD2, NSD1, NSD2, NSD3, and ASH1L. We find that H3K36me2 is the most abundant of the three methylation states and is predominantly deposited at intergenic regions by NSD1, and partly by NSD2. In contrast, H3K36me1/3 are most …


Clinical And Functional Studies Of Mtor Variants In Smith-Kingsmore Syndrome Reveal Deficits Of Circadian Rhythm And Sleep-Wake Behavior, Andrew C Liu, Yang Shen, Carolyn R Serbinski, Hongzhi He, Destino Roman, Mehari Endale, Lindsey Aschbacher-Smith, Katherine A King, Jorge L Granadillo, Isabel López, Darcy A Krueger, Thomas J Dye, David F Smith, John B Hogenesch, Carlos E Prada Oct 2024

Clinical And Functional Studies Of Mtor Variants In Smith-Kingsmore Syndrome Reveal Deficits Of Circadian Rhythm And Sleep-Wake Behavior, Andrew C Liu, Yang Shen, Carolyn R Serbinski, Hongzhi He, Destino Roman, Mehari Endale, Lindsey Aschbacher-Smith, Katherine A King, Jorge L Granadillo, Isabel López, Darcy A Krueger, Thomas J Dye, David F Smith, John B Hogenesch, Carlos E Prada

2020-Current year OA Pubs

Heterozygous de novo or inherited gain-of-function mutations in the MTOR gene cause Smith-Kingsmore syndrome (SKS). SKS is a rare autosomal dominant condition, and individuals with SKS display macrocephaly/megalencephaly, developmental delay, intellectual disability, and seizures. A few dozen individuals are reported in the literature. Here, we report a cohort of 28 individuals with SKS that represent nine MTOR pathogenic variants. We conducted a detailed natural history study and found pathophysiological deficits among individuals with SKS in addition to the common neurodevelopmental symptoms. These symptoms include sleep-wake disturbance, hyperphagia, and hyperactivity, indicative of homeostatic imbalance. To characterize these variants, we developed cell …


Lowering The Burden: Shorter Versions Of The Program Sustainability Assessment Tool (Psat) And Clinical Sustainability Assessment Tool (Csat), Sara Malone, Kim Prewitt, Virginia Mckay, Luke Zabotka, Caren Bacon, Douglas A Luke Oct 2024

Lowering The Burden: Shorter Versions Of The Program Sustainability Assessment Tool (Psat) And Clinical Sustainability Assessment Tool (Csat), Sara Malone, Kim Prewitt, Virginia Mckay, Luke Zabotka, Caren Bacon, Douglas A Luke

2020-Current year OA Pubs

BACKGROUND: Although significant advances have been made in the conceptualization of sustainability, having pragmatic, psychometrically valid tools remains a need within the field. Our previous work has developed frameworks and tools to assess both program sustainability and clinical sustainability capacity. This work presents new, psychometrically tested short versions of the Program Sustainability Assessment Tool (PSAT) and the Clinical Sustainability Assessment Tool (CSAT).

METHODS: These methods were conducted in identical, parallel processes for the CSAT and PSAT. Previously collected data for these instruments was obtained across a variety of settings, contexts, and participants. We first conducted testing to determine cronbach's alpha …


Recent Progress In Modeling And Treating Diabetes Using Stem Cell-Derived Islets, Marlie M Maestas, Maggie H Bui, Jeffrey R Millman Oct 2024

Recent Progress In Modeling And Treating Diabetes Using Stem Cell-Derived Islets, Marlie M Maestas, Maggie H Bui, Jeffrey R Millman

2020-Current year OA Pubs

Stem cell-derived islets (SC-islets) offer the potential to be an unlimited source of cells for disease modeling and the treatment of diabetes. SC-islets can be genetically modified, treated with chemical compounds, or differentiated from patient derived stem cells to model diabetes. These models provide insights into disease pathogenesis and vulnerabilities that may be targeted to provide treatment. SC-islets themselves are also being investigated as a cell therapy for diabetes. However, the transplantation process is imperfect; side effects from immunosuppressant use have reduced SC-islet therapeutic potential. Alternative methods to this include encapsulation, use of immunomodulating molecules, and genetic modification of SC-islets. …


Rethinking Our Future: Describing And Enhancing The Impacts Of Dissemination And Implementation Science For Cancer Prevention And Control, Vianca C. Soulette, Karen M. Emmons, Douglas A. Luke, Peg Allen, Bobbi J. Carothers, Ross C. Brownson Oct 2024

Rethinking Our Future: Describing And Enhancing The Impacts Of Dissemination And Implementation Science For Cancer Prevention And Control, Vianca C. Soulette, Karen M. Emmons, Douglas A. Luke, Peg Allen, Bobbi J. Carothers, Ross C. Brownson

2020-Current year OA Pubs

No abstract provided.


Molecular Characterization Of Sterol C4-Methyl Oxidase In Leishmania Major, Yu Ning, Somrita Basu, Fong-Fu Hsu, Mei Feng, Michael Zhuo Wang, Kai Zhang Oct 2024

Molecular Characterization Of Sterol C4-Methyl Oxidase In Leishmania Major, Yu Ning, Somrita Basu, Fong-Fu Hsu, Mei Feng, Michael Zhuo Wang, Kai Zhang

2020-Current year OA Pubs

Sterol biosynthesis requires the oxidative removal of two methyl groups from the C-4 position by sterol C-4-demethylase and one methyl group from the C-14 position by sterol C-14-demethylase. In


Clinical Sequelae Of Gut Microbiome Development And Disruption In Hospitalized Preterm Infants, Robert Thänert, Drew J Schwartz, Eric C Keen, Carla Hall-Moore, Bin Wang, Nurmohammad Shaikh, Jie Ning, L Colleen Rouggly-Nickless, Anna Thänert, Aura Ferreiro, Skye R S Fishbein, Janice E Sullivan, Paula Radmacher, Marilyn Escobedo, Barbara B Warner, Phillip I Tarr, Gautam Dantas Oct 2024

Clinical Sequelae Of Gut Microbiome Development And Disruption In Hospitalized Preterm Infants, Robert Thänert, Drew J Schwartz, Eric C Keen, Carla Hall-Moore, Bin Wang, Nurmohammad Shaikh, Jie Ning, L Colleen Rouggly-Nickless, Anna Thänert, Aura Ferreiro, Skye R S Fishbein, Janice E Sullivan, Paula Radmacher, Marilyn Escobedo, Barbara B Warner, Phillip I Tarr, Gautam Dantas

2020-Current year OA Pubs

Aberrant preterm infant gut microbiota assembly predisposes to early-life disorders and persistent health problems. Here, we characterize gut microbiome dynamics over the first 3 months of life in 236 preterm infants hospitalized in three neonatal intensive care units using shotgun metagenomics of 2,512 stools and metatranscriptomics of 1,381 stools. Strain tracking, taxonomic and functional profiling, and comprehensive clinical metadata identify Enterobacteriaceae, enterococci, and staphylococci as primarily exploiting available niches to populate the gut microbiome. Clostridioides difficile lineages persist between individuals in single centers, and Staphylococcus epidermidis lineages persist within and, unexpectedly, between centers. Collectively, antibiotic and non-antibiotic medications influence gut …


Activation Of Pkr By A Short-Hairpin Rna, Kyle A Cottrell, Sua Ryu, Helen Donelick, Hung Mai, Addison A Young, Jackson R Pierce, Brenda L Bass, Jason D Weber Oct 2024

Activation Of Pkr By A Short-Hairpin Rna, Kyle A Cottrell, Sua Ryu, Helen Donelick, Hung Mai, Addison A Young, Jackson R Pierce, Brenda L Bass, Jason D Weber

2020-Current year OA Pubs

Recognition of viral infection often relies on the detection of double-stranded RNA (dsRNA), a process that is conserved in many different organisms. In mammals, proteins such as MDA5, RIG-I, OAS, and PKR detect viral dsRNA, but struggle to differentiate between viral and endogenous dsRNA. This study investigates an shRNA targeting DDX54's potential to activate PKR, a key player in the immune response to dsRNA. Knockdown of DDX54 by a specific shRNA induced robust PKR activation in human cells, even when DDX54 is overexpressed, suggesting an off-target mechanism. Activation of PKR by the shRNA was enhanced by knockdown of ADAR1, a …


Rare Variant Contribution To The Heritability Of Coronary Artery Disease, Ghislain Rocheleau, Erica P Young, Nathan O Stitziel, Et Al. Oct 2024

Rare Variant Contribution To The Heritability Of Coronary Artery Disease, Ghislain Rocheleau, Erica P Young, Nathan O Stitziel, Et Al.

2020-Current year OA Pubs

Whole genome sequences (WGS) enable discovery of rare variants which may contribute to missing heritability of coronary artery disease (CAD). To measure their contribution, we apply the GREML-LDMS-I approach to WGS of 4949 cases and 17,494 controls of European ancestry from the NHLBI TOPMed program. We estimate CAD heritability at 34.3% assuming a prevalence of 8.2%. Ultra-rare (minor allele frequency ≤ 0.1%) variants with low linkage disequilibrium (LD) score contribute ~50% of the heritability. We also investigate CAD heritability enrichment using a diverse set of functional annotations: i) constraint; ii) predicted protein-altering impact; iii) cis-regulatory elements from a cell-specific chromatin …


Symposium: What Does The Microbiome Tell Us About Prevention And Treatment Of Ad/Adrd?, Joia K Capocchi, Claudia Figueroa-Romero, Sage J B Dunham, Gina Faraci, Jason A Rothman, Katrine L Whiteson, Dong-Oh Seo, David M Holtzman, Stefanie Grabrucker, Yvonne M Nolan, Rima Kaddurah-Daouk, David A Jett Oct 2024

Symposium: What Does The Microbiome Tell Us About Prevention And Treatment Of Ad/Adrd?, Joia K Capocchi, Claudia Figueroa-Romero, Sage J B Dunham, Gina Faraci, Jason A Rothman, Katrine L Whiteson, Dong-Oh Seo, David M Holtzman, Stefanie Grabrucker, Yvonne M Nolan, Rima Kaddurah-Daouk, David A Jett

2020-Current year OA Pubs

Alzheimer's disease (AD) and Alzheimer's disease-related dementias (ADRDs) are broad-impact multifactorial neurodegenerative diseases. Their complexity presents unique challenges for developing effective therapies. This review highlights research presented at the 2024 Society for Neuroscience meeting which emphasized the gut microbiome's role in AD pathogenesis by influencing brain function and neurodegeneration through the microbiota-gut-brain axis. This emerging evidence underscores the potential for targeting the gut microbiota to treat AD/ADRD.


Estimates Of Actual And Potential Lives Saved In The United States From The Use Of Covid-19 Convalescent Plasma, Quigly Dragotakes, Jeffrey P Henderson, Et Al. Oct 2024

Estimates Of Actual And Potential Lives Saved In The United States From The Use Of Covid-19 Convalescent Plasma, Quigly Dragotakes, Jeffrey P Henderson, Et Al.

2020-Current year OA Pubs

In the Spring of 2020, the United States of America (USA) deployed COVID-19 convalescent plasma (CCP) to treat hospitalized patients. Over 500,000 patients were treated with CCP during the first year of the pandemic. In this study, we estimated the number of actual inpatient lives saved by CCP treatment in the United States of America based on CCP weekly use, weekly national mortality data, and CCP mortality reduction data from meta-analyses of randomized controlled trials and real-world data. We also estimate the potential number of lives saved if CCP had been deployed for 100% of hospitalized patients or used in …


Association Of Resilience-Related Life Experiences On Variability On Age Of Onset In Dominantly Inherited Alzheimer Disease, Hye Joo Son, Randall J. Bateman, Jorge J. Llibre-Guerra, Richard J. Perrin, John C. Morris, Carlos Cruchaga, Jason Hassenstab, Alisha Daniels, Et Al. Oct 2024

Association Of Resilience-Related Life Experiences On Variability On Age Of Onset In Dominantly Inherited Alzheimer Disease, Hye Joo Son, Randall J. Bateman, Jorge J. Llibre-Guerra, Richard J. Perrin, John C. Morris, Carlos Cruchaga, Jason Hassenstab, Alisha Daniels, Et Al.

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: It remains unknown whether the associations between protective lifestyles and sporadic dementia risk reported in observational studies also affect age at symptom onset (AAO) in autosomal dominant Alzheimer disease (ADAD) with predominant genetic influences. We investigated the associations between resilience-related life experiences and interindividual AAO variability in ADAD.

METHODS: We performed a longitudinal and confirmatory analysis of the Dominantly Inherited Alzheimer Network prospective observational cohort (January 2009-June 2018, follow-up duration 2.13 ± 2.22 years), involving clinical, CSF, and lifestyle/behavioral assessments. We performed a 2-pronged comprehensive resilience assessment in each cohort. Cohort 1, incorporating the general resilience definition …


Informing Estimates Of Probability Of Clostridioides Difficile Infection For Testing And Treatment: Expert Consensus From A Modified-Delphi Procedure, Jonathan D Baghdadi, Erik R Dubberke, Michael Durkin, Jennie H Kwon, Et Al. Oct 2024

Informing Estimates Of Probability Of Clostridioides Difficile Infection For Testing And Treatment: Expert Consensus From A Modified-Delphi Procedure, Jonathan D Baghdadi, Erik R Dubberke, Michael Durkin, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

BACKGROUND:

METHODS: A panel of fifteen experts in infectious diseases participated in a modified UCLA/RAND Delphi study to estimate likelihood of CDI. Consensus, defined as agreement by >70% of panelists, was assessed via a REDCap survey. Items without consensus were discussed in a virtual meeting followed by a second survey.

RESULTS: All fifteen panelists completed both surveys (100% response rate). In the initial survey, consensus was present on 6 of 15 (40%) items related to risk of CDI. After panel discussion and clarification of questions, consensus (>70% agreement) was reached on all remaining items in the second survey. Antibiotics …


Membrane Association And Polar Localization Of The Legionella Pneumophila T4ss Doto Atpase Mediated By Two Nonredundant Receptors, Sukhithasri Vijayrajratnam, Sonja Milek, Stefano Maggi, Kaleigh Ashen, Micah Ferrell, Ahmet Hasanovic, Agnieszka Holgerson, Shanmugapriya Kannaiah, Manpreet Singh, Debnath Ghosal, Grant J Jensen, Joseph P Vogel Oct 2024

Membrane Association And Polar Localization Of The Legionella Pneumophila T4ss Doto Atpase Mediated By Two Nonredundant Receptors, Sukhithasri Vijayrajratnam, Sonja Milek, Stefano Maggi, Kaleigh Ashen, Micah Ferrell, Ahmet Hasanovic, Agnieszka Holgerson, Shanmugapriya Kannaiah, Manpreet Singh, Debnath Ghosal, Grant J Jensen, Joseph P Vogel

2020-Current year OA Pubs

The


Enhanced Staphylococcus Aureus Protection By Uncoupling Of The Α-Toxin-Adam10 Interaction During Murine Neonatal Vaccination, Kelly L Tomaszewski, Meagan Blanchard, Reuben Olaniyi, Hannah R Brenton, Samantha Hayes, Farheen Fatma, Gaya K Amarasinghe, Byoung-Kyu Cho, Young Ah Goo, Andrea C Dedent, Stephanie A Fritz, Juliane Bubeck Wardenburg Oct 2024

Enhanced Staphylococcus Aureus Protection By Uncoupling Of The Α-Toxin-Adam10 Interaction During Murine Neonatal Vaccination, Kelly L Tomaszewski, Meagan Blanchard, Reuben Olaniyi, Hannah R Brenton, Samantha Hayes, Farheen Fatma, Gaya K Amarasinghe, Byoung-Kyu Cho, Young Ah Goo, Andrea C Dedent, Stephanie A Fritz, Juliane Bubeck Wardenburg

2020-Current year OA Pubs

Staphylococcus aureus remains a leading global cause of bacterial infection-associated mortality and has eluded prior vaccine development efforts. S. aureus α-toxin (Hla) is an essential virulence factor in disease, impairing the T cell response to infection. The anti-Hla antibody response is a correlate of human protective immunity. Here we observe that this response is limited early in human life and design a vaccine strategy to elicit immune protection against Hla in a neonatal mice. By targeted disruption of the interaction of Hla with its receptor ADAM10, we identify a vaccine antigen (Hla


Impact Of Cancer Therapy On Clonal Hematopoiesis Mutations And Subsequent Clinical Outcomes, Kevin T Nead, Irenaeus C C Chan, Kelly L Bolton, Et Al. Oct 2024

Impact Of Cancer Therapy On Clonal Hematopoiesis Mutations And Subsequent Clinical Outcomes, Kevin T Nead, Irenaeus C C Chan, Kelly L Bolton, Et Al.

2020-Current year OA Pubs

Exposure to cancer therapies is associated with an increased risk of clonal hematopoiesis (CH). The objective of our study was to investigate the genesis and evolution of CH after cancer therapy. In this prospective study, we undertook error-corrected duplex DNA sequencing in blood samples collected before and at 2 time points after chemoradiation in patients with esophageal or lung cancer recruited from 2013 to 2018. We applied a customized workflow to identify the earliest changes in CH mutation count and clone size and determine their association with clinical outcomes. Our study included 29 patients (87 samples). Their median age was …


Multidimensional Profiling Of Human T Cells Reveals High Cd38 Expression, Marking Recent Thymic Emigrants And Age-Related Naive T Cell Remodeling, Pavla Bohacova, Marina Terekhova, Riley Mullins, Kamila Husarcikova, Irina Shchukina, Alina Ulezko Antonova, Barbora Echalar, Jan Kossl, Adam Saidu, Chelsea Mannie, Laura Arthur, Daniel Kreisel, Philip A Mudd, Marina Cella, Sidharth V Puram, Pirooz Eghtesady, Maxim N Artyomov, Et Al. Oct 2024

Multidimensional Profiling Of Human T Cells Reveals High Cd38 Expression, Marking Recent Thymic Emigrants And Age-Related Naive T Cell Remodeling, Pavla Bohacova, Marina Terekhova, Riley Mullins, Kamila Husarcikova, Irina Shchukina, Alina Ulezko Antonova, Barbora Echalar, Jan Kossl, Adam Saidu, Chelsea Mannie, Laura Arthur, Daniel Kreisel, Philip A Mudd, Marina Cella, Sidharth V Puram, Pirooz Eghtesady, Maxim N Artyomov, Et Al.

2020-Current year OA Pubs

Thymic involution is a key factor in human immune aging, leading to reduced thymic output and a decline in recent thymic emigrant (RTE) naive T cells in circulation. Currently, the precise definition of human RTEs and their corresponding cell surface markers lacks clarity. Analysis of single-cell RNA-seq/ATAC-seq data distinguished RTEs by the expression of SOX4, IKZF2, and TOX and CD38 protein, whereby surface CD38


Xenotransplanted Human Organoids Identify Transepithelial Zinc Transport As A Key Mediator Of Intestinal Adaptation, Maame Efua S Sampah, Vered Gazit, Deborah C Rubin, Et Al. Oct 2024

Xenotransplanted Human Organoids Identify Transepithelial Zinc Transport As A Key Mediator Of Intestinal Adaptation, Maame Efua S Sampah, Vered Gazit, Deborah C Rubin, Et Al.

2020-Current year OA Pubs

Short bowel syndrome (SBS) leads to severe morbidity and mortality. Intestinal adaptation is crucial in improving outcomes. To understand the human gene pathways associated with adaptation, we perform single-cell transcriptomic analysis of human small intestinal organoids explanted from mice with experimental SBS. We show that transmembrane ion pathways, specifically the transepithelial zinc transport pathway genes SLC39A4 and SLC39A5, are upregulated in SBS. This discovery is corroborated by an external dataset, bulk RT-qPCR, and Western blots. Oral zinc supplementation is shown to improve survival and weight gain of SBS mice and increase the proliferation of intestinal crypt cells in vitro. Finally, …


An Iron-Rich Subset Of Macrophages Promotes Tumor Growth Through A Bach1-Ednrb Axis, Ian W Folkert, Mai T Dang, Et Al. Oct 2024

An Iron-Rich Subset Of Macrophages Promotes Tumor Growth Through A Bach1-Ednrb Axis, Ian W Folkert, Mai T Dang, Et Al.

2020-Current year OA Pubs

We define a subset of macrophages in the tumor microenvironment characterized by high intracellular iron and enrichment of heme and iron metabolism genes. These iron-rich tumor-associated macrophages (iTAMs) supported angiogenesis and immunosuppression in the tumor microenvironment and were conserved between mice and humans. iTAMs comprise two additional subsets based on gene expression profile and location-perivascular (pviTAM) and stromal (stiTAM). We identified the endothelin receptor type B (Ednrb) as a specific marker of iTAMs and found myeloid-specific deletion of Ednrb to reduce tumor growth and vascular density. Further studies identified the transcription factor Bach1 as a repressor of the iTAM transcriptional …


Human Epidemiology And Response To Sars-Cov-2 (Heros): Objectives, Design, And Enrollment Results Of A 12-City Remote Observational Surveillance Study Of Households With Children, Using Direct-To-Participant Methods, Patricia C Fulkerson, Katherine Rivera-Spoljaric, Et Al. Oct 2024

Human Epidemiology And Response To Sars-Cov-2 (Heros): Objectives, Design, And Enrollment Results Of A 12-City Remote Observational Surveillance Study Of Households With Children, Using Direct-To-Participant Methods, Patricia C Fulkerson, Katherine Rivera-Spoljaric, Et Al.

2020-Current year OA Pubs

The Human Epidemiology and Response to SARS-CoV-2 (HEROS) Study is a prospective, multicity, 6-month incidence study conducted from May 2020 to February 2021. The objectives were to identify risk factors for SARS-CoV-2 infection and household transmission among children and people with asthma and allergic diseases, and to use the host nasal transcriptome sampled longitudinally to understand infection risk and sequelae at the molecular level. To overcome challenges of clinical study implementation due to the coronavirus pandemic, this surveillance study used direct-to-participant methods to remotely enroll and prospectively follow eligible children who are participants in other National Institutes of Health-funded pediatric …


Machine Learning And Bayesian Network Analyses Identifies Associations With Insomnia In A National Sample Of 31,285 Treatment-Seeking College Students, Adam Calderon, Seung Yeon Baik, Matthew H S Ng, Ellen E Fitzsimmons-Craft, Daniel Eisenberg, Denise E Wilfley, C Barr Taylor, Michelle G Newman Oct 2024

Machine Learning And Bayesian Network Analyses Identifies Associations With Insomnia In A National Sample Of 31,285 Treatment-Seeking College Students, Adam Calderon, Seung Yeon Baik, Matthew H S Ng, Ellen E Fitzsimmons-Craft, Daniel Eisenberg, Denise E Wilfley, C Barr Taylor, Michelle G Newman

2020-Current year OA Pubs

BACKGROUND: A better understanding of the relationships between insomnia and anxiety, mood, eating, and alcohol-use disorders is needed given its prevalence among young adults. Supervised machine learning provides the ability to evaluate which mental disorder is most associated with heightened insomnia among U.S. college students. Combined with Bayesian network analysis, probable directional relationships between insomnia and interacting symptoms may be illuminated.

METHODS: The current exploratory analyses utilized a national sample of college students across 26 U.S. colleges and universities collected during population-level screening before entering a randomized controlled trial. We used a 4-step statistical approach: (1) at the disorder level, …


25-Hydroxycholesterol Promotes Brain Cytokine Production And Leukocyte Infiltration In A Mouse Model Of Lipopolysaccharide-Induced Neuroinflammation, Johnathan Romero, Danira Toral-Rios, Jinsheng Yu, Steven M Paul, Anil G Cashikar Oct 2024

25-Hydroxycholesterol Promotes Brain Cytokine Production And Leukocyte Infiltration In A Mouse Model Of Lipopolysaccharide-Induced Neuroinflammation, Johnathan Romero, Danira Toral-Rios, Jinsheng Yu, Steven M Paul, Anil G Cashikar

2020-Current year OA Pubs

Neuroinflammation has been implicated in the pathogenesis of several neurologic and psychiatric disorders. Microglia are key drivers of neuroinflammation and, in response to different inflammatory stimuli, overexpress a proinflammatory signature of genes. Among these, Ch25h is a gene overexpressed in brain tissue from Alzheimer's disease as well as various mouse models of neuroinflammation. Ch25h encodes cholesterol 25-hydroxylase, an enzyme upregulated in activated microglia under conditions of neuroinflammation, that hydroxylates cholesterol to form 25-hydroxycholesterol (25HC). 25HC can be further metabolized to 7α,25-dihydroxycholesterol, which is a potent chemoattractant of leukocytes. We have previously shown that 25HC increases the production and secretion of …


Genetic And Clinical Correlates Of Two Neuroanatomical Ai Dimensions In The Alzheimer's Disease Continuum, Junhao Wen, Aristeidis Sotiras, Daniel S Marcus, Pamela Lamontagne, Tammie L Benzinger, John C Morris, Et Al. Oct 2024

Genetic And Clinical Correlates Of Two Neuroanatomical Ai Dimensions In The Alzheimer's Disease Continuum, Junhao Wen, Aristeidis Sotiras, Daniel S Marcus, Pamela Lamontagne, Tammie L Benzinger, John C Morris, Et Al.

2020-Current year OA Pubs

Alzheimer's disease (AD) is associated with heterogeneous atrophy patterns. We employed a semi-supervised representation learning technique known as Surreal-GAN, through which we identified two latent dimensional representations of brain atrophy in symptomatic mild cognitive impairment (MCI) and AD patients: the "diffuse-AD" (R1) dimension shows widespread brain atrophy, and the "MTL-AD" (R2) dimension displays focal medial temporal lobe (MTL) atrophy. Critically, only R2 was associated with widely known sporadic AD genetic risk factors (e.g., APOE ε4) in MCI and AD patients at baseline. We then independently detected the presence of the two dimensions in the early stages by deploying the trained …


Nationwide Availability Of And Enrollment In Medicare And Medicaid Dual-Eligible Special Needs Plans With Exclusively Aligned Enrollment, Kenton J Johnston, Michelle Hendricks, Megha Dabas, Eliza Macneal, Jeah Jung, David J Meyers, Jose F Figueroa, Eric T Roberts Oct 2024

Nationwide Availability Of And Enrollment In Medicare And Medicaid Dual-Eligible Special Needs Plans With Exclusively Aligned Enrollment, Kenton J Johnston, Michelle Hendricks, Megha Dabas, Eliza Macneal, Jeah Jung, David J Meyers, Jose F Figueroa, Eric T Roberts

2020-Current year OA Pubs

IMPORTANCE: In 2021, the Centers for Medicare & Medicaid Services designated a new category of dual-eligible special needs plans (D-SNPs) with exclusively aligned enrollment (receive Medicare and Medicaid benefits through the same plan or affiliated plans within the same organization).

OBJECTIVE: To assess the availability of and enrollment in D-SNPs with exclusively aligned enrollment and to compare the characteristics of beneficiaries enrolled in D-SNPs with exclusively aligned enrollment available vs beneficiaries without such enrollment available.

DESIGN, SETTING, AND PARTICIPANTS: Full-benefit beneficiaries enrolled in D-SNPs for 6 months or longer in 2021 or 2022. Availability of and beneficiary enrollment in D-SNPs …