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The Association Of Caregiver Attitudes, Information Sources, And Trust With Hpv Vaccine Initiation Among Adolescents, Akila Anandarajah, Thembekile Shato, Sarah Humble, Alan R Barnette, Heather M Brandt, Lisa M Klesges, Vetta L Sanders Thompson, Michelle I Silver Dec 2024

The Association Of Caregiver Attitudes, Information Sources, And Trust With Hpv Vaccine Initiation Among Adolescents, Akila Anandarajah, Thembekile Shato, Sarah Humble, Alan R Barnette, Heather M Brandt, Lisa M Klesges, Vetta L Sanders Thompson, Michelle I Silver

2020-Current year OA Pubs

This study described caregiver attitudes and the information sources they access about HPV vaccination for adolescents and determined their influence on human papillomavirus (HPV) vaccination initiation. An online survey was administered to 1,016 adults in July 2021. Participants were eligible if they were the caregiver of a child aged 9-17 residing in Mississippi, Arkansas, Tennessee, Missouri, and select counties in Southern Illinois. Multivariate logistic regression was used to estimate the association of caregiver attitudes and information sources with HPV vaccination. Information from doctors or healthcare providers (87.4%) and internet sources other than social media (31.0%) were the most used sources …


Saponin Tql1055 Adjuvant-Containing Vaccine Confers Protection Upon Mycobacterium Tuberculosis Challenge In Mice, Mushtaq Ahmed, Eric Farris, Rosemary V Swanson, Shibali Das, Yan Yang, Tyler Martin, Shabaana A Khader Dec 2024

Saponin Tql1055 Adjuvant-Containing Vaccine Confers Protection Upon Mycobacterium Tuberculosis Challenge In Mice, Mushtaq Ahmed, Eric Farris, Rosemary V Swanson, Shibali Das, Yan Yang, Tyler Martin, Shabaana A Khader

2020-Current year OA Pubs

Tuberculosis (TB), caused by the intracellular pathogen


Emergent Microenvironments Of Nucleoli, Matthew R King, Kiersten M Ruff, Rohit V Pappu Dec 2024

Emergent Microenvironments Of Nucleoli, Matthew R King, Kiersten M Ruff, Rohit V Pappu

2020-Current year OA Pubs

In higher eukaryotes, the nucleolus harbors at least three sub-phases that facilitate multiple functionalities including ribosome biogenesis. The three prominent coexisting sub-phases are the fibrillar center (FC), the dense fibrillar component (DFC), and the granular component (GC). Here, we review recent efforts in profiling sub-phase compositions that shed light on the types of physicochemical properties that emerge from compositional biases and territorial organization of specific types of macromolecules. We highlight roles played by molecular grammars which refers to protein sequence features including the substrate binding domains, the sequence features of intrinsically disordered regions, and the multivalence of these distinct types …


Evaluation Of Prognostic Factors In Patients With High-Risk Classical Hodgkin Lymphoma Undergoing Autologous Transplantation, Narendranath Epperla, Amanda F Cashen, Et Al. Nov 2024

Evaluation Of Prognostic Factors In Patients With High-Risk Classical Hodgkin Lymphoma Undergoing Autologous Transplantation, Narendranath Epperla, Amanda F Cashen, Et Al.

2020-Current year OA Pubs

There are limited data assessing the risk scores for primary treatment failure (PTF) in patients with classical Hodgkin lymphoma (cHL; PTF-cHL) undergoing autologous hematopoietic cell transplantation (auto-HCT). ECLIPSE (Evaluation of Classical Hodgkin Lymphoma patients wIth Primary treatment failure and analySis of outcomEs) is a multicenter retrospective cohort of patients with PTF-cHL (aged ≥15 years) diagnosed on or after 1 January 2005, at 15 US medical centers. PTF was defined as 1 of the following patterns of failure: (1) progressive disease by imaging during or within 6 weeks of completion of frontline chemotherapy (primary progression [PP]); (2) partial response (PR) or …


Iglon5 Frequency In Idiopathic Rem Sleep Behavior Disorder: A Multicenter Study, Ronald Postuma, Jennifer Mcleland, Albert A. Davis, Yo-El S. Ju, Et Al. Nov 2024

Iglon5 Frequency In Idiopathic Rem Sleep Behavior Disorder: A Multicenter Study, Ronald Postuma, Jennifer Mcleland, Albert A. Davis, Yo-El S. Ju, Et Al.

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: Idiopathic/isolated REM sleep behavior disorder (iRBD) has been strongly linked to neurodegenerative synucleinopathies such as Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. However, there have been increasing reports of RBD as a presenting feature of serious and treatable autoimmune syndromes, particularly IGLON5. This study's objective was to investigate the frequency of autoantibodies in a large cohort of participants with iRBD.

METHODS: Participants were enrolled in the North American Prodromal Synucleinopathy cohort with polysomnography-confirmed iRBD, free of parkinsonism and dementia. Plasma samples were systematically screened for the autoantibodies IGLON5, DPPX, LGI1, and CASPR2 using plasma …


Impact Of An Individualized Pain Plan To Treat Sickle Cell Disease Vaso-Occlusive Episodes In The Emergency Department, Lauren Siewny, Allison King, Cathy L Melvin, Christopher R Carpenter, Jane S Hankins, Joseph S Colla, Liliana Preiss, Lingzi Luo, Lisa Cox, Marsha Treadwell, Natalia Davila, Rita V Masese, Sarah Mccuskee, S Siera Gollan, Paula Tanabe Oct 2024

Impact Of An Individualized Pain Plan To Treat Sickle Cell Disease Vaso-Occlusive Episodes In The Emergency Department, Lauren Siewny, Allison King, Cathy L Melvin, Christopher R Carpenter, Jane S Hankins, Joseph S Colla, Liliana Preiss, Lingzi Luo, Lisa Cox, Marsha Treadwell, Natalia Davila, Rita V Masese, Sarah Mccuskee, S Siera Gollan, Paula Tanabe

2020-Current year OA Pubs

To address acute vaso-occlusive episodes (VOEs), the leading cause of emergency department (ED) visits among individuals with sickle cell disease (SCD), we conducted the clinical study, ALIGN (An Individualized Pain Plan with Patient and Provider Access for Emergency Department care of SCD), across 8 sites. We hypothesized an improvement of 0.5 standard deviations in perceived quality of ED pain treatment of a VOE after implementing individualized pain plans (IPPs) accessible to both patients and providers. Patients with SCD were aged 18 to 45 years, owned a cell phone, and had an ED VOE visit within 90 days prior. Patients completed …


Gene-Specific Effects On Brain Volume And Cognition Of Tmem106b In Frontotemporal Lobar Degeneration, Marijne Vandebergh, Nupur Ghoshal, Et Al. Oct 2024

Gene-Specific Effects On Brain Volume And Cognition Of Tmem106b In Frontotemporal Lobar Degeneration, Marijne Vandebergh, Nupur Ghoshal, Et Al.

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES:

METHODS: Participants were enrolled through the ARTFL/LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) study, which includes symptomatic and presymptomatic individuals with a pathogenic variant in

RESULTS: The minor allele of

DISCUSSION: We identified associations of


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. …


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 …


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 …


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 …


A New Era Of Data-Driven Cancer Research And Care: Opportunities And Challenges, Felicia Gomez, Arpad M Danos, Joshua F Mcmichael, Malachi Griffith, Obi L Griffith, Et Al. Oct 2024

A New Era Of Data-Driven Cancer Research And Care: Opportunities And Challenges, Felicia Gomez, Arpad M Danos, Joshua F Mcmichael, Malachi Griffith, Obi L Griffith, Et Al.

2020-Current year OA Pubs

People diagnosed with cancer and their formal and informal caregivers are increasingly faced with a deluge of complex information, thanks to rapid advancements in the type and volume of diagnostic, prognostic, and treatment data. This commentary discusses the opportunities and challenges that the society faces as we integrate large volumes of data into regular cancer care.


Cell Type-Specific Epigenetic Priming Of Gene Expression In Nucleus Accumbens By Cocaine, Philipp Mews, Yentl Van Der Zee, Ashik Gurung, Molly Estill, Rita Futamura, Hope Kronman, Aarthi Ramakrishnan, Meagan Ryan, Abner A Reyes, Benjamin A Garcia, Caleb J Browne, Simone Sidoli, Li Shen, Eric J Nestler Oct 2024

Cell Type-Specific Epigenetic Priming Of Gene Expression In Nucleus Accumbens By Cocaine, Philipp Mews, Yentl Van Der Zee, Ashik Gurung, Molly Estill, Rita Futamura, Hope Kronman, Aarthi Ramakrishnan, Meagan Ryan, Abner A Reyes, Benjamin A Garcia, Caleb J Browne, Simone Sidoli, Li Shen, Eric J Nestler

2020-Current year OA Pubs

A hallmark of addiction is the ability of drugs of abuse to trigger relapse after periods of prolonged abstinence. Here, we describe an epigenetic mechanism whereby chronic cocaine exposure causes lasting chromatin and downstream transcriptional modifications in the nucleus accumbens (NAc), a critical brain region controlling motivation. We link prolonged withdrawal from cocaine to the depletion of the histone variant H2A.Z, coupled with increased genome accessibility and latent priming of gene transcription, in D1 dopamine receptor-expressing medium spiny neurons (D1 MSNs) that relate to aberrant gene expression upon drug relapse. The histone chaperone ANP32E removes H2A.Z from chromatin, and we …


Structural Basis For Adhesin Secretion By The Outer-Membrane Usher In Type 1 Pili, Ryan M Bitter, Maxwell I Zimmerman, Brock T Summers, Jerome S Pinkner, Karen W Dodson, Scott J Hultgren, Peng Yuan Oct 2024

Structural Basis For Adhesin Secretion By The Outer-Membrane Usher In Type 1 Pili, Ryan M Bitter, Maxwell I Zimmerman, Brock T Summers, Jerome S Pinkner, Karen W Dodson, Scott J Hultgren, Peng Yuan

2020-Current year OA Pubs

Gram-negative bacteria produce chaperone-usher pathway pili, which are extracellular protein fibers tipped with an adhesive protein that binds to a receptor with stereochemical specificity to determine host and tissue tropism. The outer-membrane usher protein, together with a periplasmic chaperone, assembles thousands of pilin subunits into a highly ordered pilus fiber. The tip adhesin in complex with its cognate chaperone activates the usher to allow extrusion across the outer membrane. The structural requirements to translocate the adhesin through the usher pore from the periplasm to the extracellular space remains incompletely understood. Here, we present a cryoelectron microscopy structure of a quaternary …


Early Detection Of Malignant And Premalignant Peripheral Nerve Tumors Using Cell-Free Dna Fragmentomics, R Taylor Sundby, Paul A Jones, Divya Srihari, Amy E Armstrong, Stacey Chamberlain, Sanita Burgic, Kara Weekley, John S A Chrisinger, Angela C Hirbe, Et Al. Oct 2024

Early Detection Of Malignant And Premalignant Peripheral Nerve Tumors Using Cell-Free Dna Fragmentomics, R Taylor Sundby, Paul A Jones, Divya Srihari, Amy E Armstrong, Stacey Chamberlain, Sanita Burgic, Kara Weekley, John S A Chrisinger, Angela C Hirbe, Et Al.

2020-Current year OA Pubs

PURPOSE: Early detection of neurofibromatosis type 1 (NF1)-associated peripheral nerve sheath tumors (PNST) informs clinical decision-making, enabling early definitive treatment and potentially averting deadly outcomes. In this study, we describe a cell-free DNA (cfDNA) fragmentomic approach that distinguishes nonmalignant, premalignant, and malignant forms of PNST in the cancer predisposition syndrome, NF1.

EXPERIMENTAL DESIGN: cfDNA was isolated from plasma samples of a novel cohort of 101 patients with NF1 and 21 healthy controls and underwent whole-genome sequencing. We investigated diagnosis-specific signatures of copy-number alterations with in silico size selection as well as fragment profiles. Fragmentomics were analyzed using complementary feature types: …


Adherence To Hygiene Protocols And Doxycycline Therapy In Ameliorating Lymphatic Filariasis Morbidity In An Endemic Area Post-Interruption Of Disease Transmission In Ghana, Linda Batsa Debrah, Philip J Budge, Et Al. Oct 2024

Adherence To Hygiene Protocols And Doxycycline Therapy In Ameliorating Lymphatic Filariasis Morbidity In An Endemic Area Post-Interruption Of Disease Transmission In Ghana, Linda Batsa Debrah, Philip J Budge, Et Al.

2020-Current year OA Pubs

Filarial lymphedema (LE) remains a significant global problem despite the progress made toward elimination of lymphatic filariasis (LF). In Ghana, the main approach to LF is preventive chemotherapy, but this has minimal impact on individuals who have already developed LE. In 2018-2020, a 24-month randomized, double-blind, placebo-controlled trial was conducted to evaluate the efficacy of stringent hygiene measures using the Essential Package of Care with or without additional administration of doxycycline (DOX) to improve filarial leg LE. This study enrolled 356 participants with LE stages 1-3 from two districts in the Upper East Region of Ghana. In addition to regular …


A Retrospective Assessment Of Guideline Adherence And Treatment Outcomes From Clostridioides Difficile Infection Following The Idsa 2021 Clinical Guideline Update: Clostridioides Difficile Infection, Erik R Dubberke, Qinghua Li, Engels N Obi, Vladimir Turzhitsky, Fakhar Siddiqui, Brian H Nathanson Oct 2024

A Retrospective Assessment Of Guideline Adherence And Treatment Outcomes From Clostridioides Difficile Infection Following The Idsa 2021 Clinical Guideline Update: Clostridioides Difficile Infection, Erik R Dubberke, Qinghua Li, Engels N Obi, Vladimir Turzhitsky, Fakhar Siddiqui, Brian H Nathanson

2020-Current year OA Pubs

BACKGROUND: The 2021 update to the Infectious Diseases Society of America

METHODS: This retrospective, observational study used the PINC AI Healthcare Database on adult patients who received CDI treatment between 1/2020 and 6/2021 (pre period) and between 10/2021 and 9/2022 (post period). We examined treatment patterns of fidaxomicin, vancomycin, and metronidazole, as well as clinical and health care resource use outcomes of patients treated exclusively with fidaxomicin vs vancomycin, using nearest-neighbor propensity matching and hierarchical regression methods. As a sensitivity analysis, we repeated the fidaxomicin vs vancomycin comparisons among patients with recurrent and nonrecurrent index infections.

RESULTS: A total of …


Sequential Early-Life Viral Infections Modulate The Microbiota And Adaptive Immune Responses To Systemic And Mucosal Vaccination, Yuhao Li, Jerome M. Molleston, Crystal Lovato, Jasmine Wright, Isabel Erickson, Duyen Bui, Andrew H. Kim, Harshad Ingle, Somya Aggarwal, Lila S Nolan, Ahmed O. Hassan, Lynne Foster, Michael S. Diamond, Megan T. Baldridge Oct 2024

Sequential Early-Life Viral Infections Modulate The Microbiota And Adaptive Immune Responses To Systemic And Mucosal Vaccination, Yuhao Li, Jerome M. Molleston, Crystal Lovato, Jasmine Wright, Isabel Erickson, Duyen Bui, Andrew H. Kim, Harshad Ingle, Somya Aggarwal, Lila S Nolan, Ahmed O. Hassan, Lynne Foster, Michael S. Diamond, Megan T. Baldridge

2020-Current year OA Pubs

Increasing evidence points to the microbial exposome as a critical factor in maturing and shaping the host immune system, thereby influencing responses to immune challenges such as infections or vaccines. To investigate the effect of early-life viral exposures on immune development and vaccine responses, we inoculated mice with six distinct viral pathogens in sequence beginning in the neonatal period, and then evaluated their immune signatures before and after intramuscular or intranasal vaccination against SARS-CoV-2. Sequential viral infection drove profound changes in all aspects of the immune system, including increasing circulating leukocytes, altering innate and adaptive immune cell lineages in tissues, …


Network-Level Enrichment Provides A Framework For Biological Interpretation Of Machine Learning Results, Jiaqi Li, Ari Segel, Xinyang Feng, Jiaxin Cindy Tu, Andy Eck, Kelsey T King, Babatunde Adeyemo, Nicole R Karcher, Likai Chen, Adam T Eggebrecht, Muriah D Wheelock Oct 2024

Network-Level Enrichment Provides A Framework For Biological Interpretation Of Machine Learning Results, Jiaqi Li, Ari Segel, Xinyang Feng, Jiaxin Cindy Tu, Andy Eck, Kelsey T King, Babatunde Adeyemo, Nicole R Karcher, Likai Chen, Adam T Eggebrecht, Muriah D Wheelock

2020-Current year OA Pubs

Machine learning algorithms are increasingly being utilized to identify brain connectivity biomarkers linked to behavioral and clinical outcomes. However, research often prioritizes prediction accuracy at the expense of biological interpretability, and inconsistent implementation of ML methods may hinder model accuracy. To address this, our paper introduces a network-level enrichment approach, which integrates brain system organization in the context of connectome-wide statistical analysis to reveal network-level links between brain connectivity and behavior. To demonstrate the efficacy of this approach, we used linear support vector regression (LSVR) models to examine the relationship between resting-state functional connectivity networks and chronological age. We compared …


Leveraging Gpt-4 For Identifying Cancer Phenotypes In Electronic Health Records: A Performance Comparison Between Gpt-4, Gpt-3.5-Turbo, Flan-T5, Llama-3-8b, And Spacy's Rule-Based And Machine Learning-Based Methods, Kriti Bhattarai, Inez Y Oh, Jonathan Moran Sierra, Jonathan Tang, Philip R O Payne, Zach Abrams, Albert M Lai Oct 2024

Leveraging Gpt-4 For Identifying Cancer Phenotypes In Electronic Health Records: A Performance Comparison Between Gpt-4, Gpt-3.5-Turbo, Flan-T5, Llama-3-8b, And Spacy's Rule-Based And Machine Learning-Based Methods, Kriti Bhattarai, Inez Y Oh, Jonathan Moran Sierra, Jonathan Tang, Philip R O Payne, Zach Abrams, Albert M Lai

2020-Current year OA Pubs

OBJECTIVE: Accurately identifying clinical phenotypes from Electronic Health Records (EHRs) provides additional insights into patients' health, especially when such information is unavailable in structured data. This study evaluates the application of OpenAI's Generative Pre-trained Transformer (GPT)-4 model to identify clinical phenotypes from EHR text in non-small cell lung cancer (NSCLC) patients. The goal was to identify disease stages, treatments and progression utilizing GPT-4, and compare its performance against GPT-3.5-turbo, Flan-T5-xl, Flan-T5-xxl, Llama-3-8B, and 2 rule-based and machine learning-based methods, namely, scispaCy and medspaCy.

MATERIALS AND METHODS: Phenotypes such as initial cancer stage, initial treatment, evidence of cancer recurrence, and affected …


Pkmyt1 Is A Marker Of Treatment Response And A Therapeutic Target For Cdk4/6 Inhibitor-Resistance In Er+ Breast Cancer, Anran Chen, Cynthia X Ma, Et Al. Oct 2024

Pkmyt1 Is A Marker Of Treatment Response And A Therapeutic Target For Cdk4/6 Inhibitor-Resistance In Er+ Breast Cancer, Anran Chen, Cynthia X Ma, Et Al.

2020-Current year OA Pubs

Endocrine therapies (ET) with cyclin-dependent kinase 4/6 (CDK4/6) inhibition are the standard treatment for estrogen receptor-α-positive (ER+) breast cancer, however drug resistance is common. In this study, proteogenomic analyses of patient-derived xenografts (PDXs) from patients with 22 ER+ breast cancer demonstrated that protein kinase, membrane-associated tyrosine/threonine one (PKMYT1), a WEE1 homolog, is estradiol (E2) regulated in E2-dependent PDXs and constitutively expressed when growth is E2-independent. In clinical samples, high PKMYT1 mRNA levels associated with resistance to both ET and CDK4/6 inhibition. The PKMYT1 inhibitor lunresertib (RP-6306) with gemcitabine selectively and synergistically reduced the viability of ET and palbociclib-resistant ER+ breast …


A Modular Chemigenetic Calcium Indicator For Multiplexed In Vivo Functional Imaging, Helen Farrants, Christian Monroy Hernandez, Yao Chen, Et Al. Oct 2024

A Modular Chemigenetic Calcium Indicator For Multiplexed In Vivo Functional Imaging, Helen Farrants, Christian Monroy Hernandez, Yao Chen, Et Al.

2020-Current year OA Pubs

Genetically encoded fluorescent calcium indicators allow cellular-resolution recording of physiology. However, bright, genetically targetable indicators that can be multiplexed with existing tools in vivo are needed for simultaneous imaging of multiple signals. Here we describe WHaloCaMP, a modular chemigenetic calcium indicator built from bright dye-ligands and protein sensor domains. Fluorescence change in WHaloCaMP results from reversible quenching of the bound dye via a strategically placed tryptophan. WHaloCaMP is compatible with rhodamine dye-ligands that fluoresce from green to near-infrared, including several that efficiently label the brain in animals. When bound to a near-infrared dye-ligand, WHaloCaMP shows a 7× increase in fluorescence …


Mucosal Adenovirus Vaccine Boosting Elicits Iga And Durably Prevents Xbb.1.16 Infection In Nonhuman Primates, Matthew Gagne, James Brett Case, Igor P Dmitriev, Elena A Kashentseva, Baoling Ying, David T Curiel, Michael S Diamond, Et Al. Oct 2024

Mucosal Adenovirus Vaccine Boosting Elicits Iga And Durably Prevents Xbb.1.16 Infection In Nonhuman Primates, Matthew Gagne, James Brett Case, Igor P Dmitriev, Elena A Kashentseva, Baoling Ying, David T Curiel, Michael S Diamond, Et Al.

2020-Current year OA Pubs

A mucosal route of vaccination could prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication at the site of infection and limit transmission. We compared protection against heterologous XBB.1.16 challenge in nonhuman primates (NHPs) ~5 months following intramuscular boosting with bivalent mRNA encoding WA1 and BA.5 spike proteins or mucosal boosting with a WA1-BA.5 bivalent chimpanzee adenoviral-vectored vaccine delivered by intranasal or aerosol device. NHPs boosted by either mucosal route had minimal virus replication in the nose and lungs, respectively. By contrast, protection by intramuscular mRNA was limited to the lower airways. The mucosally delivered vaccine elicited durable airway IgG …


Cross-Ancestry Genetic Investigation Of Schizophrenia, Cannabis Use Disorder, And Tobacco Smoking, Emma C Johnson, Isabelle Austin-Zimmerman, Hayley H A Thorpe, Daniel F Levey, David A A Baranger, Sarah M C Colbert, Ditte Demontis, Jibran Y Khokhar, Lea K Davis, Howard J Edenberg, Marta Di Forti, Sandra Sanchez-Roige, Joel Gelernter, Arpana Agrawal Oct 2024

Cross-Ancestry Genetic Investigation Of Schizophrenia, Cannabis Use Disorder, And Tobacco Smoking, Emma C Johnson, Isabelle Austin-Zimmerman, Hayley H A Thorpe, Daniel F Levey, David A A Baranger, Sarah M C Colbert, Ditte Demontis, Jibran Y Khokhar, Lea K Davis, Howard J Edenberg, Marta Di Forti, Sandra Sanchez-Roige, Joel Gelernter, Arpana Agrawal

2020-Current year OA Pubs

Individuals with schizophrenia frequently experience co-occurring substance use, including tobacco smoking and heavy cannabis use, and substance use disorders. There is interest in understanding the extent to which these relationships are causal, and to what extent shared genetic factors play a role. We explored the relationships between schizophrenia (Scz; European ancestry N = 161,405; African ancestry N = 15,846), cannabis use disorder (CanUD; European ancestry N = 886,025; African ancestry N = 120,208), and ever-regular tobacco smoking (Smk; European ancestry N = 805,431; African ancestry N = 24,278) using the largest available genome-wide studies of these phenotypes in individuals of …


Himal: Multimodal Hierarchical Multi-Task Auxiliary Learning Framework For Predicting Alzheimer's Disease Progression, Sayantan Kumar, Sean C Yu, Andrew Michelson, Thomas Kannampallil, Philip R O Payne Oct 2024

Himal: Multimodal Hierarchical Multi-Task Auxiliary Learning Framework For Predicting Alzheimer's Disease Progression, Sayantan Kumar, Sean C Yu, Andrew Michelson, Thomas Kannampallil, Philip R O Payne

2020-Current year OA Pubs

OBJECTIVE: We aimed to develop and validate a novel multimodal framework

MATERIALS AND METHODS: HiMAL utilized multimodal longitudinal visit data including imaging features, cognitive assessment scores, and clinical variables from MCI patients in the Alzheimer's Disease Neuroimaging Initiative dataset, to predict at each visit if an MCI patient will progress to AD within the next 6 months. Performance of HiMAL was compared with state-of-the-art single-task and multitask baselines using area under the receiver operator curve (AUROC) and precision recall curve (AUPRC) metrics. An ablation study was performed to assess the impact of each input modality on model performance. Additionally, longitudinal …


Crinophagic Granules In Pancreatic Β Cells Contribute To Mouse Autoimmune Diabetes By Diversifying Pathogenic Epitope Repertoire, Hao Hu, Anthony N Vomund, Orion J Peterson, Neetu Srivastava, Tiandao Li, Lisa Kain, Wandy L Beatty, Bo Zhang, Chyi-Song Hsieh, Luc Teyton, Cheryl F Lichti, Emil R Unanue, Xiaoxiao Wan Sep 2024

Crinophagic Granules In Pancreatic Β Cells Contribute To Mouse Autoimmune Diabetes By Diversifying Pathogenic Epitope Repertoire, Hao Hu, Anthony N Vomund, Orion J Peterson, Neetu Srivastava, Tiandao Li, Lisa Kain, Wandy L Beatty, Bo Zhang, Chyi-Song Hsieh, Luc Teyton, Cheryl F Lichti, Emil R Unanue, Xiaoxiao Wan

2020-Current year OA Pubs

Autoimmune attack toward pancreatic β cells causes permanent loss of glucose homeostasis in type 1 diabetes (T1D). Insulin secretory granules store and secrete insulin but are also thought to be tissue messengers for T1D. Here, we show that the crinophagic granules (crinosome), a minor set of vesicles formed by fusing lysosomes with the conventional insulin dense-core granules (DCG), are pathogenic in T1D development in mouse models. Pharmacological inhibition of crinosome formation in β cells delays T1D progression without affecting the dominant DCGs. Mechanistically, crinophagy inhibition diminishes the epitope repertoire in pancreatic islets, including cryptic, modified and disease-relevant epitopes derived from …


Length-Scale Study In Deep Learning Prediction For Non-Small Cell Lung Cancer Brain Metastasis, Haowen Zhou, Siyu Lin, Mark Watson, Cory T Bernadt, Oumeng Zhang, Ling Liao, Ramaswamy Govindan, Richard J Cote, Changhuei Yang Sep 2024

Length-Scale Study In Deep Learning Prediction For Non-Small Cell Lung Cancer Brain Metastasis, Haowen Zhou, Siyu Lin, Mark Watson, Cory T Bernadt, Oumeng Zhang, Ling Liao, Ramaswamy Govindan, Richard J Cote, Changhuei Yang

2020-Current year OA Pubs

Deep learning-assisted digital pathology has demonstrated the potential to profoundly impact clinical practice, even surpassing human pathologists in performance. However, as deep neural network (DNN) architectures grow in size and complexity, their explainability decreases, posing challenges in interpreting pathology features for broader clinical insights into physiological diseases. To better assess the interpretability of digital microscopic images and guide future microscopic system design, we developed a novel method to study the predictive feature length-scale that underpins a DNN's predictive power. We applied this method to analyze a DNN's capability in predicting brain metastasis from early-stage non-small-cell lung cancer biopsy slides. This …


A Basally Active Cgas-Sting Pathway Limits Sars-Cov-2 Replication In A Subset Of Ace2 Positive Airway Cell Models, Maritza Puray-Chavez, Jenna E Eschbach, Ming Xia, Kyle M Lapak, Qianzi Zhou, Ria Jasuja, Jiehong Pan, Jian Xu, Zixiang Zhou, Shawn Mohammed, Qibo Wang, Dana Q Lawson, Sanja Djokic, Gaopeng Hou, Siyuan Ding, Steven L Brody, Michael B Major, Dennis Goldfarb, Sebla B Kutluay Sep 2024

A Basally Active Cgas-Sting Pathway Limits Sars-Cov-2 Replication In A Subset Of Ace2 Positive Airway Cell Models, Maritza Puray-Chavez, Jenna E Eschbach, Ming Xia, Kyle M Lapak, Qianzi Zhou, Ria Jasuja, Jiehong Pan, Jian Xu, Zixiang Zhou, Shawn Mohammed, Qibo Wang, Dana Q Lawson, Sanja Djokic, Gaopeng Hou, Siyuan Ding, Steven L Brody, Michael B Major, Dennis Goldfarb, Sebla B Kutluay

2020-Current year OA Pubs

Host factors that define the cellular tropism of SARS-CoV-2 beyond the cognate ACE2 receptor are poorly defined. Here we report that SARS-CoV-2 replication is restricted at a post-entry step in a number of ACE2-positive airway-derived cell lines due to tonic activation of the cGAS-STING pathway mediated by mitochondrial DNA leakage and naturally occurring cGAS and STING variants. Genetic and pharmacological inhibition of the cGAS-STING and type I/III IFN pathways as well as ACE2 overexpression overcome these blocks. SARS-CoV-2 replication in STING knockout cell lines and primary airway cultures induces ISG expression but only in uninfected bystander cells, demonstrating efficient antagonism …


Nur77 Protects The Bladder Urothelium From Intracellular Bacterial Infection, Christina A Collins, Chevaughn Waller, Ekaterina Batourina, Lokesh Kumar, Cathy L Mendelsohn, Nicole M Gilbert Sep 2024

Nur77 Protects The Bladder Urothelium From Intracellular Bacterial Infection, Christina A Collins, Chevaughn Waller, Ekaterina Batourina, Lokesh Kumar, Cathy L Mendelsohn, Nicole M Gilbert

2020-Current year OA Pubs

Intracellular infections by Gram-negative bacteria are a significant global health threat. The nuclear receptor Nur77 (also called TR3, NGFI-B, or NR4A1) was recently shown to sense cytosolic bacterial lipopolysaccharide (LPS). However, the potential role for Nur77 in controlling intracellular bacterial infection has not been examined. Here we show that Nur77 protects against intracellular infection in the bladder by uropathogenic Escherichia coli (UPEC), the leading cause of urinary tract infections (UTI). Nur77 deficiency in mice promotes the formation of UPEC intracellular bacterial communities (IBCs) in the cells lining the bladder lumen, leading to persistent infection in bladder tissue. Conversely, treatment with …


Durations Of Antibiotic Treatment For Acute Otitis Media And Variability In Prescribed Durations Across Two Large Academic Health Systems, Sophie E Katz, Timothy C Jenkins, Amy B Stein, Gale Thomas, Nancy Koenig, Gary Lucas Starnes, Jason G Newland, Ritu Banerjee, Holly M Frost Sep 2024

Durations Of Antibiotic Treatment For Acute Otitis Media And Variability In Prescribed Durations Across Two Large Academic Health Systems, Sophie E Katz, Timothy C Jenkins, Amy B Stein, Gale Thomas, Nancy Koenig, Gary Lucas Starnes, Jason G Newland, Ritu Banerjee, Holly M Frost

2020-Current year OA Pubs

BACKGROUND: Acute otitis media (AOM) accounts for roughly 25% of antibiotics prescribed to children annually. Despite national guidelines that recommend short (5-7 days) durations of antibiotics for children 2 years and older with AOM, most receive long (10 day) courses. This study aims to evaluate antibiotic durations prescribed for children aged 2-17 years with uncomplicated AOM across two pediatric academic health systems, and to assess the variability in prescribed durations between and within each system.

METHODS: Electronic medical record data from 135 care locations at two health systems were retrospectively analyzed. Outpatient encounters for children aged 2-17 years with a …