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Patient-Generated Health Data: Impact On Promoting Patient-Centered Point Of Care Tobacco Treatment In Patients With Cancer, Jessica Liu, Jingling Chen, Nina Smock, Nicholas B Griffith, Ramaswamy Govindan, Paula Goldberg, Jodi Thole, Kristin Daly, James Reddy, Alex T Ramsey, Laura J Bierut, Aimee James, Robert A Schnoll, Ross C Brownson, Li-Shiun Chen, Et Al. Apr 2025

Patient-Generated Health Data: Impact On Promoting Patient-Centered Point Of Care Tobacco Treatment In Patients With Cancer, Jessica Liu, Jingling Chen, Nina Smock, Nicholas B Griffith, Ramaswamy Govindan, Paula Goldberg, Jodi Thole, Kristin Daly, James Reddy, Alex T Ramsey, Laura J Bierut, Aimee James, Robert A Schnoll, Ross C Brownson, Li-Shiun Chen, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Guideline-based tobacco treatment is infrequently offered. Electronic health record-enabled patient-generated health data (PGHD) has the potential to increase patient treatment engagement and satisfaction.

METHODS: We evaluated outcomes of a strategy to enable PGHD in a medical oncology clinic from July 1, 2021 to December 31, 2022. Among 12,777 patients, 82.1% received a tobacco screener about use and interest in treatment as part of eCheck-in via the patient portal.

RESULTS: We attained a broad reach (82.1%) and moderate response rate (30.9%) for this low-burden PGHD strategy. Patients reporting current smoking (

DISCUSSION: PGHD via patient portal appears to be a …


Perspectives On The Current Diagnostic And Treatment Paradigms In Secondary Hemophagocytic Lymphohistiocytosis (Hlh), Leonard Naymagon, Jeffrey Bednarski, Et Al. Apr 2025

Perspectives On The Current Diagnostic And Treatment Paradigms In Secondary Hemophagocytic Lymphohistiocytosis (Hlh), Leonard Naymagon, Jeffrey Bednarski, Et Al.

2020-Current year OA Pubs

Improved awareness of hemophagocytic lymphohistiocytosis (HLH) among clinicians has led to an increase in its diagnosis. Often diagnosis is made based on the HLH- 2004 criteria. While these criteria have considerable strengths, they lack specificity and may be fulfilled in the setting of many pro-inflammatory disorders. Genetic defects affecting cellular cytotoxicity cause familial (primary) HLH. On the other hand, secondary HLH is more a pathophysiologic process common to many conditions, rather than a singular disease entity. Improved genetic, immunologic, and functional testing have changed not only the way we diagnose HLH, but also how we treat it. In 2004, there …


Comparative Efficacy And Acceptability Of Interventions For Universal, Selective And Indicated Prevention Of Eating Disorders: Study Protocol For A Systematic Review And Network Meta-Analysis, Sandra Schlegl, Felicitas Hirler, Andreas Gerich, Mikkel Højlund, Eric Stice, Tracey Wade, Denise Wilfley, James Downs, Ulrich Voderholzer, Jasmine Perry, Verena Haas, Marco Solmi, Christoph Correll Apr 2025

Comparative Efficacy And Acceptability Of Interventions For Universal, Selective And Indicated Prevention Of Eating Disorders: Study Protocol For A Systematic Review And Network Meta-Analysis, Sandra Schlegl, Felicitas Hirler, Andreas Gerich, Mikkel Højlund, Eric Stice, Tracey Wade, Denise Wilfley, James Downs, Ulrich Voderholzer, Jasmine Perry, Verena Haas, Marco Solmi, Christoph Correll

2020-Current year OA Pubs

BACKGROUND: Eating disorders (EDs) are severe psychiatric conditions, with prevalence rates ranging from 5.5 to 17.9% in women and 0.6 to 2.4% in men. EDs carry a high risk of chronicity and mortality, highlighting the need for effective prevention strategies. Primary prevention can target the entire population (universal), high-risk groups (selective), or individuals with early signs (indicated). Despite substantial research, prior reviews often show limitations, such as single-author data extraction, lack of quality assessment, reliance on endpoint data, exclusion of obesity prevention programs, or outdated findings. No review has yet evaluated the comparative effectiveness of multiple interventions across risk groups. …


Adipose-Derived Leptin And Complement Factor D Mediate Osteoarthritis Severity And Pain, Kelsey H Collins, Kristin L Lenz, Hope D Welhaven, Erica Ely, Luke E Springer, Sophie Paradi, Ruhang Tang, Lauryn Braxton, Antonina Akk, Huimin Yan, Bo Zhang, Xiaobo Wu, John P Atkinson, Arin K Oestreich, Ron K June, Christine T N Pham, Farshid Guilak Apr 2025

Adipose-Derived Leptin And Complement Factor D Mediate Osteoarthritis Severity And Pain, Kelsey H Collins, Kristin L Lenz, Hope D Welhaven, Erica Ely, Luke E Springer, Sophie Paradi, Ruhang Tang, Lauryn Braxton, Antonina Akk, Huimin Yan, Bo Zhang, Xiaobo Wu, John P Atkinson, Arin K Oestreich, Ron K June, Christine T N Pham, Farshid Guilak

2020-Current year OA Pubs

Obesity is a risk factor for osteoarthritis (OA), and leptin is among the adipokines implicated in obesity-induced OA. However, the specific role of leptin in OA severity and pain is not known. Using lipodystrophic (LD) mice, we show that fat-secreted factors are required for knee OA development, implicating a fat-cartilage cross-talk. Fat pad implantation or systemic leptin restoration in LD mice reintroduced structural OA and pain, whereas implantation of leptin-deficient fat pad did not change OA susceptibility. Isochronic parabiosis and spatial transcriptomics confirmed that a fat-joint cross-talk likely occurred via soluble mediators. Global unsupervised multiomics of conditioned media from fat …


Development And Evaluation Of A Non-Invasive Brain-Spine Interface Using Transcutaneous Spinal Cord Stimulation, Carolyn Atkinson, Lorenzo Lombardi, Meredith Lang, Rodolfo Keesey, Rachel Hawthorn, Zachary Seitz, Eric C Leuthardt, Peter Brunner, Ismael Seáñez Apr 2025

Development And Evaluation Of A Non-Invasive Brain-Spine Interface Using Transcutaneous Spinal Cord Stimulation, Carolyn Atkinson, Lorenzo Lombardi, Meredith Lang, Rodolfo Keesey, Rachel Hawthorn, Zachary Seitz, Eric C Leuthardt, Peter Brunner, Ismael Seáñez

2020-Current year OA Pubs

Motor rehabilitation is a therapeutic process to facilitate functional recovery in people with spinal cord injury (SCI). However, its efficacy is limited to areas with remaining sensorimotor function. Spinal cord stimulation (SCS) creates a temporary prosthetic effect that may allow further rehabilitation-induced recovery in individuals without remaining sensorimotor function, thereby extending the therapeutic reach of motor rehabilitation to individuals with more severe injuries. In this work, we report our first steps in developing a non-invasive brain-spine interface (BSI) based on electroencephalography (EEG) and transcutaneous spinal cord stimulation (tSCS). The objective of this study was to identify EEG-based neural correlates of …


Functional Screening Identifies Kinesin Spindle Protein Inhibitor Filanesib As A Potential Treatment Option For Hepatoblastoma, Ruth Nousiainen, Katja Eloranta, Jani Saarela, Antti Hassinen, Tamara J Luck, Stefano Cairo, Emilie Indersie, Swapnil Potdar, Michaela J Feodoroff, Jouko Lohi, Lassi Paavolainen, David B Wilson, Vilja Pietiäinen, Markku Heikinheimo, Marjut Pihlajoki Apr 2025

Functional Screening Identifies Kinesin Spindle Protein Inhibitor Filanesib As A Potential Treatment Option For Hepatoblastoma, Ruth Nousiainen, Katja Eloranta, Jani Saarela, Antti Hassinen, Tamara J Luck, Stefano Cairo, Emilie Indersie, Swapnil Potdar, Michaela J Feodoroff, Jouko Lohi, Lassi Paavolainen, David B Wilson, Vilja Pietiäinen, Markku Heikinheimo, Marjut Pihlajoki

2020-Current year OA Pubs

Hepatoblastoma is a rare pediatric liver malignancy usually treated with surgery and chemotherapy. To explore new treatment options for hepatoblastoma, drug screening was performed using six cell models established from aggressive hepatoblastoma tumors and healthy pediatric primary hepatocytes. Of the 527 screened compounds, 98 demonstrated cancer-selective activity in at least one hepatoblastoma model. The kinesin spindle protein (KSP) inhibitor filanesib was effective in all models and was further evaluated. Filanesib induced G2/M arrest and apoptosis in hepatoblastoma cells at concentrations tolerable to primary hepatocytes. Prominent nuclear fragmentation was observed in filanesib-treated hepatoblastoma cells. Genes participating in cell cycle regulation were …


Deciphering Distinct Genetic Risk Factors For Ftld-Tdp Pathological Subtypes Via Whole-Genome Sequencing, Cyril Pottier, Carlos Cruchaga, Et Al. Apr 2025

Deciphering Distinct Genetic Risk Factors For Ftld-Tdp Pathological Subtypes Via Whole-Genome Sequencing, Cyril Pottier, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

Frontotemporal lobar degeneration with neuronal inclusions of the TAR DNA-binding protein 43 (FTLD-TDP) is a fatal neurodegenerative disorder with only a limited number of risk loci identified. We report our comprehensive genome-wide association study as part of the International FTLD-TDP Whole-Genome Sequencing Consortium, including 985 patients and 3,153 controls compiled from 26 institutions/brain banks in North America, Europe and Australia, and meta-analysis with the Dementia-seq cohort. We confirm UNC13A as the strongest overall FTLD-TDP risk factor and identify TNIP1 as a novel FTLD-TDP risk factor. In subgroup analyzes, we further identify genome-wide significant loci specific to each of the three …


Implementation Of The Extension For Community Healthcare Outcomes Model For Hypertension Education Of Frontline Health Care Workers In The Federal Capital Territory, Nigeria: Explanatory Sequential Mixed Methods Evaluation, Abigail S Baldridge, Mark D Huffman, Et Al. Apr 2025

Implementation Of The Extension For Community Healthcare Outcomes Model For Hypertension Education Of Frontline Health Care Workers In The Federal Capital Territory, Nigeria: Explanatory Sequential Mixed Methods Evaluation, Abigail S Baldridge, Mark D Huffman, Et Al.

2020-Current year OA Pubs

BACKGROUND: The Extension for Community Healthcare Outcomes (ECHO) model was adapted for hypertension education of community health extension workers in the Federal Capital Territory, Nigeria, and delivered as a 7-part series.

OBJECTIVE: This study aims to evaluate implementation outcomes of the hypertension ECHO series mapped to the first 3 levels of the Kirkpatrick model. Outcomes included reach, appropriateness (level 1), effectiveness (level 2), and penetration (level 3).

METHODS: From August 2022 to April 2023, 7 hypertension ECHO sessions were delivered via Zoom (Zoom Video Communications, Inc) to a health care worker audience including targeted community health extension workers at 12 …


Induction Of Cardiac Fibulin-4 Protects Against Pressure Overload-Induced Cardiac Hypertrophy And Heart Failure, E D Van Deel, C M Halabi, Et Al. Apr 2025

Induction Of Cardiac Fibulin-4 Protects Against Pressure Overload-Induced Cardiac Hypertrophy And Heart Failure, E D Van Deel, C M Halabi, Et Al.

2020-Current year OA Pubs

The prevailing view of fibulin-4 deficient mice is that the cardiac phenotype is the result of aortic and/or valvular disease. In the present study, we have tested whether the cardiac phenotype is, at least in part, the consequence of primary cardiac effects of fibulin-4. We have found fibulin-4 expression to be activated throughout the myocardium in wildtype (fibulin-4


Sars-Cov-2 N Protein And Anti-Spike Serologies: Insights Into Covid-19 Disease Severity And Mortality-A Secondary Analysis Of The Activ-1 Trial, Alfredo J Mena Lora, Kimi Enders, Huimin Wu, Luis Parra-Rodriguez, Christopher Palma, Katy Saliba, Sylvain Laverdurre, P Brian Smith, Kevin J Anstrom, Samuel A Bozzette, William G Powderly Apr 2025

Sars-Cov-2 N Protein And Anti-Spike Serologies: Insights Into Covid-19 Disease Severity And Mortality-A Secondary Analysis Of The Activ-1 Trial, Alfredo J Mena Lora, Kimi Enders, Huimin Wu, Luis Parra-Rodriguez, Christopher Palma, Katy Saliba, Sylvain Laverdurre, P Brian Smith, Kevin J Anstrom, Samuel A Bozzette, William G Powderly

2020-Current year OA Pubs

BACKGROUND: Understanding factors that predict progression to severe COVID-19 is critical. Antibodies targeting SARS-CoV-2 spike protein confer protection, while the N protein of SARS-CoV-2 plays roles in viral replication and immune dysfunction. This study explores the significance of N protein and anti-spike antibodies on disease severity, progression, and mortality.

OBJECTIVES: To evaluate the relationship between SARS-CoV-2 N protein and anti-spike antibody levels with disease severity, clinical outcomes, and mortality in hospitalized patients with COVID-19.

DESIGN: A secondary analysis of serologic data from participants in the ACTIV-1 randomized clinical trial, which evaluated immunomodulators for the treatment of hospitalized patients with COVID-19. …


Disuse-Driven Plasticity In The Human Thalamus And Putamen, Roselyne J Chauvin, Dillan J Newbold, Ashley N Nielsen, Ryland L Miller, Samuel R Krimmel, Athanasia Metoki, Anxu Wang, Andrew N Van, David F Montez, Scott Marek, Vahdeta Suljic, Noah J Baden, Nadeshka Ramirez-Perez, Kristen M Scheidter, Julia S Monk, Forrest I Whiting, Babatunde Adeyemo, Jarod L Roland, Abraham Z Snyder, Benjamin P Kay, Marcus E Raichle, Timothy O Laumann, Evan M Gordon, Nico U F Dosenbach Apr 2025

Disuse-Driven Plasticity In The Human Thalamus And Putamen, Roselyne J Chauvin, Dillan J Newbold, Ashley N Nielsen, Ryland L Miller, Samuel R Krimmel, Athanasia Metoki, Anxu Wang, Andrew N Van, David F Montez, Scott Marek, Vahdeta Suljic, Noah J Baden, Nadeshka Ramirez-Perez, Kristen M Scheidter, Julia S Monk, Forrest I Whiting, Babatunde Adeyemo, Jarod L Roland, Abraham Z Snyder, Benjamin P Kay, Marcus E Raichle, Timothy O Laumann, Evan M Gordon, Nico U F Dosenbach

2020-Current year OA Pubs

Subcortical plasticity has mainly been studied using invasive electrophysiology in animals. Here, we leverage precision functional mapping (PFM) to study motor plasticity in the human subcortex during 2 weeks of upper-extremity immobilization with daily resting-state and motor task fMRI. We found previously that, in the cortex, limb disuse drastically impacts disused primary motor cortex functional connectivity (FC) and is associated with spontaneous fMRI pulses. It remains unknown whether disuse-driven plasticity pulses and FC changes are cortex specific or whether they could also affect movement-critical nodes in the thalamus and striatum. Tailored analysis methods now show spontaneous disuse pulses and FC …


Samd9 Senses Cytosolic Double-Stranded Nucleic Acids In Epithelial And Mesenchymal Cells To Induce Antiviral Immunity, Gaopeng Hou, Wandy Beatty, Juhee Son, Yinxing Zhu, Qingyu Sheng, Wanyi Huang, Dian Li, Constin Liu, Chen Shen, L David Sibley, Siyuan Ding, Et Al. Apr 2025

Samd9 Senses Cytosolic Double-Stranded Nucleic Acids In Epithelial And Mesenchymal Cells To Induce Antiviral Immunity, Gaopeng Hou, Wandy Beatty, Juhee Son, Yinxing Zhu, Qingyu Sheng, Wanyi Huang, Dian Li, Constin Liu, Chen Shen, L David Sibley, Siyuan Ding, Et Al.

2020-Current year OA Pubs

Sensing of cytosolic, double-stranded (ds) DNA or dsRNA molecules derived from microbial or endogenous sources triggers cell-intrinsic innate immunity, but sensors recognizing both cytosolic dsDNA and dsRNA are sparsely reported. Here we find that full-length human SAMD9 protein directly binds to synthetic or viral dsDNA or dsRNA. Overexpression of SAMD9 from various vertebrate species leads to robust production of interferons and pro-inflammatory cytokines. By contrast, loss of endogenous SAMD9 impairs the interferon responses to cytosolic dsDNA and dsRNA stimulation in multiple cell types and enhances the infectivity of pathogenic dsDNA and dsRNA viruses. Mice lacking Samd9l, the human SAMD9 homolog, …


Center-Ing Black Voices: Incorporating Lived Experience Across The Research Process To Advance Equity In Drug Treatment And Outcomes, Devin E Banks, Maria E Paschke, Kaytryn D Campbell, Daje D Bradshaw-Glenn, Rashmi Ghonasgi, Burton Barr, Arial Collins, Gerald Dennis, Keith Lofton, Alfred Long, Harriet Montgomery, Andreas Prince, Rachel P Winograd Apr 2025

Center-Ing Black Voices: Incorporating Lived Experience Across The Research Process To Advance Equity In Drug Treatment And Outcomes, Devin E Banks, Maria E Paschke, Kaytryn D Campbell, Daje D Bradshaw-Glenn, Rashmi Ghonasgi, Burton Barr, Arial Collins, Gerald Dennis, Keith Lofton, Alfred Long, Harriet Montgomery, Andreas Prince, Rachel P Winograd

2020-Current year OA Pubs

BACKGROUND: Black people in the United States face persistent and increasing inequities in addiction treatment access and drug overdose death. Incorporating people with lived experience through community based participatory research (CBPR) approaches can improve understanding of drivers of and solutions to such inequities. However, practical and systemic challenges limit incorporating Black people with lived experience with substance use across each step of the research process. This paper describes the methods, recommendations, and lessons learned from a research team and Black-led community advisory board (CAB) working together across the research process to promote equity in harm reduction and addiction treatment.

METHODS: …


Mendelian Randomization Study Of Sleep Traits And Risk Of Colorectal Cancer, Olympia Dimopoulou, Yin Cao, Et Al. Apr 2025

Mendelian Randomization Study Of Sleep Traits And Risk Of Colorectal Cancer, Olympia Dimopoulou, Yin Cao, Et Al.

2020-Current year OA Pubs

A potential association of endogenous circadian rhythm disruption with risk of cancer development has been suggested, however, epidemiological evidence for the association of sleep traits with colorectal cancer (CRC) is limited and often contradictory. Here we investigated whether genetically predicted chronotype, insomnia and sleep duration are associated with CRC risk in males, females and overall and according to CRC anatomical subsites using Mendelian randomization (MR). The two-sample inverse variance weighted (IVW) method was applied using summary-level data in up to 58,221 CRC cases and 67,694 controls and genome-wide association data of genetic variants for self-reported sleep traits. Secondary analyses using …


Molecular Mechanism Establishing The Off Pathway In Vision, Florentina Soto, Chin-I Lin, Andrew Jo, Ssu-Yu Chou, Ellen G Harding, Philip A Ruzycki, Gail K Seabold, Ronald S Petralia, Daniel Kerschensteiner Apr 2025

Molecular Mechanism Establishing The Off Pathway In Vision, Florentina Soto, Chin-I Lin, Andrew Jo, Ssu-Yu Chou, Ellen G Harding, Philip A Ruzycki, Gail K Seabold, Ronald S Petralia, Daniel Kerschensteiner

2020-Current year OA Pubs

Parallel ON and OFF (positive- and negative-contrast) pathways fundamental to vision arise at the complex synapse of cone photoreceptors. Cone pedicles form spatially segregated functionally opposite connections with ON and OFF bipolar cells. Here, we discover that mammalian cones express LRFN2, a cell-adhesion molecule, which localizes to the pedicle base. LRFN2 stabilizes basal contacts between cone pedicles and OFF bipolar cell dendrites to guide pathway-specific partner choices, encompassing multiple cell types. In addition, LRFN2 trans-synaptically organizes glutamate receptor clusters, determining the contrast preferences of the OFF pathway. ON and OFF pathways converge in the inner retina to regulate bipolar cell …


Determining Potential Immunomodulatory Drug Efficacy In Sepsis Using Elispot, Andrew H Walton, Dale F Osborne, Ethan B Davitt, Anne M Drewry, Richard S Hotchkiss, Et Al. Apr 2025

Determining Potential Immunomodulatory Drug Efficacy In Sepsis Using Elispot, Andrew H Walton, Dale F Osborne, Ethan B Davitt, Anne M Drewry, Richard S Hotchkiss, Et Al.

2020-Current year OA Pubs

This study evaluated the ability of ELISpot to identify potential immuno-modulatory drug therapies in sepsis. ELISpot was performed ex vivo on whole blood from septic patients and healthy controls. Innate and adaptive immunity were evaluated by production of TNF-α and IFN-γ, respectively. Drug efficacy was determined by their effects to modulate the both the number of cytokine-producing cells and amount of cytokine produced per cell. The corticosteroid dexamethasone was evaluated for its ability to down modulate TNF-α and IFN-γ production. The TLR7/8 agonist resiquimod (R848) and T cell stimulants IL-7 and anti-PD-1 mAb were tested for their ability to enhance …


Injured Tubular Epithelia-Derived Ccn1 Promotes The Mobilization Of Fibroblasts Toward Injury Sites After Kidney Injury, Tomohiro Nakata, Benjamin D Humphreys, Et Al. Apr 2025

Injured Tubular Epithelia-Derived Ccn1 Promotes The Mobilization Of Fibroblasts Toward Injury Sites After Kidney Injury, Tomohiro Nakata, Benjamin D Humphreys, Et Al.

2020-Current year OA Pubs

Humoral factors that prompt fibroblasts to migrate to an injury site at an appropriate time point are deemed indispensable for repair after kidney injury. We herein demonstrated the pivotal roles of injured tubule-derived cellular communication network factor 1 (CCN1) in the mobilization of fibroblasts to the injury site after kidney injury. Based on analyses of ligand-receptor interactions


Enhancement Of The Endocannabinoid System Through Monoacylglycerol Lipase Inhibition Relieves Migraine-Associated Pain In Mice, Elizaveta Mangutov, Yaseen Awad-Igbaria, Kendra Siegersma, Francois Gastambide, Ayodeji A Asuni, Amynah A A Pradhan Apr 2025

Enhancement Of The Endocannabinoid System Through Monoacylglycerol Lipase Inhibition Relieves Migraine-Associated Pain In Mice, Elizaveta Mangutov, Yaseen Awad-Igbaria, Kendra Siegersma, Francois Gastambide, Ayodeji A Asuni, Amynah A A Pradhan

2020-Current year OA Pubs

BACKGROUND: Migraine affects over 1 billion people worldwide and is a leading cause of disability. Targeting the cannabinoid system offers a promising approach for pain and migraine relief. This study evaluated a novel monoacylglycerol lipase (MAGL) inhibitor to prolong endocannabinoid action in acute and chronic mouse models of migraine. It also examined MAGL and cannabinoid receptor 1 (CB

METHODS: C57BL6/J male and female mice received the human migraine trigger nitroglycerin (NTG) acutely or every other day for 9 days. Allodynia was assessed by von Frey hair stimulation of the periorbital area. A single dose of MAGL inhibitor (ABD-1970) was tested …


Mechanism Of Dna Replication Fork Breakage And Parp1 Hyperactivation During Replication Catastrophe, Pedro Ortega, Elodie Bournique, Junyi Li, Ambrocio Sanchez, Gisselle Santiago, Brooke R Harris, Josefine Striepen, John Maciejowski, Abby M Green, Rémi Buisson Apr 2025

Mechanism Of Dna Replication Fork Breakage And Parp1 Hyperactivation During Replication Catastrophe, Pedro Ortega, Elodie Bournique, Junyi Li, Ambrocio Sanchez, Gisselle Santiago, Brooke R Harris, Josefine Striepen, John Maciejowski, Abby M Green, Rémi Buisson

2020-Current year OA Pubs

Ataxia telangiectasia and Rad3-related (ATR) inhibition triggers a surge in origin firing, resulting in increased levels of single-stranded DNA (ssDNA) that rapidly deplete all available RPA. This leaves ssDNA unprotected and susceptible to breakage, a phenomenon known as replication catastrophe. However, the mechanism by which unprotected ssDNA breaks remains unclear. Here, we reveal that APOBEC3B is the key enzyme targeting unprotected ssDNA at replication forks, initiating a reaction cascade that induces fork collapse and poly(ADP-ribose) polymerase 1 (PARP1) hyperactivation. Mechanistically, we demonstrate that uracils generated by APOBEC3B at replication forks are removed by UNG2, resulting in abasic sites that are …


Brain-Like Border Ownership Signals Support Prediction Of Natural Videos, Zeyuan Ye, Ralf Wessel, Tom P Franken Apr 2025

Brain-Like Border Ownership Signals Support Prediction Of Natural Videos, Zeyuan Ye, Ralf Wessel, Tom P Franken

2020-Current year OA Pubs

To make sense of visual scenes, the brain must segment foreground from background. This is thought to be facilitated by neurons that signal border ownership (BOS), which indicate which side of a border in their receptive field is owned by an object. How these signals emerge without a teaching signal of what is foreground remains unclear. Here we find that many units in PredNet, a self-supervised deep neural network trained to predict future frames in natural videos, are selective for BOS. They share key properties with BOS neurons in the brain, including robustness to object transformations and hysteresis. Ablation revealed …


Asynchronous Development Of The Mouse Auditory Cortex Is Driven By Hemispheric Identity And Sex, Ashlan P Reid, Demetrios Neophytou, Robert Levy, Cody Pham, Hysell V Oviedo Apr 2025

Asynchronous Development Of The Mouse Auditory Cortex Is Driven By Hemispheric Identity And Sex, Ashlan P Reid, Demetrios Neophytou, Robert Levy, Cody Pham, Hysell V Oviedo

2020-Current year OA Pubs

Lateralized auditory processing is essential for specialized functions such as speech processing, typically dominated by the Left Auditory Cortex (ACx) in humans. Hemispheric specializations also occur in the adult mouse ACx, but their developmental origins are unclear. Our study finds that the Left and Right ACx in mice reach developmental milestones at different ages. Thalamocortical responses and maturation of synaptic dynamics develop earlier in the Right ACx than the Left. We show that this timing offset predicts hemisphere-dependent differences in sensory-driven plasticity. Juvenile tone exposure at specific times results in imbalanced adult tone frequency representations in the Right and Left …


The Essential Calcium Channel Of Sperm Catsper Is Temperature-Gated, Dilip K Swain, Citlalli Vergara, Júlia Castro-Arnau, Polina V Lishko Apr 2025

The Essential Calcium Channel Of Sperm Catsper Is Temperature-Gated, Dilip K Swain, Citlalli Vergara, Júlia Castro-Arnau, Polina V Lishko

2020-Current year OA Pubs

The flagellar calcium channel CatSper is essential for male fertility, as it regulates calcium influx to trigger the hyperactive motility required for sperm to fertilize the egg. Precise activation of CatSper is critical, as premature activation can impair sperm function. While optimal temperature is known to influence fertilization, its effect on CatSper remains unknown. By directly recording from mouse spermatozoa, we reveal that CatSper functions as a temperature-gated ion channel, with a thermal threshold of 33.5 °C and a temperature coefficient Q


Prevalence Of Medical Writing In Hematological Malignancy Review Articles, Héctor A Vaquera-Alfaro, Elham Nasrollahi, Yashvin Onkarappa Mangala, David Russler-Germain, Aaron Goodman, Ghulam Rehman Mohyuddin Apr 2025

Prevalence Of Medical Writing In Hematological Malignancy Review Articles, Héctor A Vaquera-Alfaro, Elham Nasrollahi, Yashvin Onkarappa Mangala, David Russler-Germain, Aaron Goodman, Ghulam Rehman Mohyuddin

2020-Current year OA Pubs

BACKGROUND: Medical writing services, initially developed to streamline manuscript preparation, have raised ethical concerns due to their association with industry influence and spin. While prevalent in oncology and malignant hematology clinical trials, medical writing involvement in review articles remains underexplored, particularly in the hematology literature. Furthermore, conflict of interests of the writers may also affect the content of review articles. This study investigates the prevalence, characteristics, and funding sources of medical writing in malignant hematology review articles and their relationship with the financial conflicts of interest (CoI) among authors.

METHODS: We conducted a cross-sectional analysis of review articles published in …


Age-Related Meningeal Extracellular Matrix Remodeling Compromises Cns Lymphatic Function, Kate Hitpass Romero, Taylor J Stevenson, Leon C D Smyth, Ben Watkin, Samuel J C Mccullough, Luca Vinnell, Amy M Smith, Patrick Schweder, Jason A Correia, Jonathan Kipnis, Mike Dragunow, Justin Rustenhoven Apr 2025

Age-Related Meningeal Extracellular Matrix Remodeling Compromises Cns Lymphatic Function, Kate Hitpass Romero, Taylor J Stevenson, Leon C D Smyth, Ben Watkin, Samuel J C Mccullough, Luca Vinnell, Amy M Smith, Patrick Schweder, Jason A Correia, Jonathan Kipnis, Mike Dragunow, Justin Rustenhoven

2020-Current year OA Pubs

Efficient clearance of central nervous system (CNS) waste proteins and appropriate immune surveillance is essential for brain health. These processes are facilitated by lymphatic networks present in the meninges that drain cerebrospinal fluid (CSF). Age-related impairments to meningeal lymphatic drainage contribute to CNS waste accumulation and immune dysfunction, yet the underlying mechanisms remain poorly understood. Here, we identify extracellular matrix (ECM) remodeling in the aged dura as a key driver of CSF clearance deficits, demonstrating that peri-lymphatic collagen accumulation disrupts lymphatic function. Exploring immune-derived factors contributing to this ECM remodeling, we identify transforming growth factor beta 1 (TGFβ1) as a …


Elevated Mitochondrial Membrane Potential Is A Therapeutic Vulnerability In Dnmt3a-Mutant Clonal Hematopoiesis, Kira A Young, Grant A Challen, Et Al. Apr 2025

Elevated Mitochondrial Membrane Potential Is A Therapeutic Vulnerability In Dnmt3a-Mutant Clonal Hematopoiesis, Kira A Young, Grant A Challen, Et Al.

2020-Current year OA Pubs

The competitive advantage of mutant hematopoietic stem and progenitor cells (HSPCs) underlies clonal hematopoiesis (CH). Drivers of CH include aging and inflammation; however, how CH-mutant cells gain a selective advantage in these contexts is an unresolved question. Using a murine model of CH (Dnmt3a


Imaging Peripheral Nerves In Vivo With Ct Neurogram Using Novel 2,4,6-Tri-Iodinated Lidocaine Contrast Agent, Rui Tang, Ron Perez, David M Brogan, Mikhail Y Berezin, James E Mccarthy Apr 2025

Imaging Peripheral Nerves In Vivo With Ct Neurogram Using Novel 2,4,6-Tri-Iodinated Lidocaine Contrast Agent, Rui Tang, Ron Perez, David M Brogan, Mikhail Y Berezin, James E Mccarthy

2020-Current year OA Pubs

Peripheral nerve injuries are a significant concern in surgical procedures, often leading to chronic pain and functional impairment. Despite advancements in imaging, preoperative and intraoperative visualization of peripheral nerves remains a challenge. This study introduces and evaluates a novel tri-iodinated lidocaine-based contrast agent for computed tomography neurography, aiming to enhance the intraoperative visibility of peripheral nerves in vivo. A tri-iodinated lidocaine analogue was synthesized and characterized for its radiodensity, sodium channel binding and nerve affinity. Sodium channel affinity was performed using molecular docking. In vitro contrast enhancement was assessed by comparing the agent's Hounsfield unit (HU) values with those of …


Immunotherapeutic Strategies In Head And Neck Cancer: Challenges And Opportunities, Xia Liu, R. Alex Harbison, Mark A. Varvares, Sidharth V. Puram, Guangyong Peng Apr 2025

Immunotherapeutic Strategies In Head And Neck Cancer: Challenges And Opportunities, Xia Liu, R. Alex Harbison, Mark A. Varvares, Sidharth V. Puram, Guangyong Peng

2020-Current year OA Pubs

HNSCC remains a substantial health issue, with treatment options including surgery, radiation, and platinum-based chemotherapy. Unfortunately, despite progress in research, only modest gains have been made in disease control, with existing treatments resulting in significant functional and quality-of-life issues. The introduction of immunotherapy in the treatment of HNSCC has resulted in some improvements in outlook for patients and is now standard of care for populations with both recurrent and metastatic disease. However, despite the early successes, responses to immune checkpoint inhibition (ICI) remain modest to low, approaching 14%-22% objective response rates. Challenges to the effectiveness of ICI and other immunotherapies …


Understanding Implementation Determinants Of Universal School Meals Through An Equity-Driven Mixed Methods Approach, Gabriella M Mcloughlin, Molly Kerstetter, Yerusalem Yohannes, Omar Martinez, Resa M Jones, Ross C Brownson, Jennifer O Fisher Apr 2025

Understanding Implementation Determinants Of Universal School Meals Through An Equity-Driven Mixed Methods Approach, Gabriella M Mcloughlin, Molly Kerstetter, Yerusalem Yohannes, Omar Martinez, Resa M Jones, Ross C Brownson, Jennifer O Fisher

2020-Current year OA Pubs

BACKGROUND: Policies, such as Universal School Meals (USM), are essential for preventing inequities in chronic disease risk among socially and economically marginalized populations. Implementing USM reduces food insecurity and obesity risk, among other academic/health outcomes; unfortunately, across the nation student participation (i.e., reach) is lower than expected, limiting its public health impact. Grounded in implementation science and health equity frameworks, this study aimed to: 1) investigate the determinants of implementing USM in a large, urban school district and 2) assess key challenges and supports across schools with varying levels of participation in USM.

METHODS: A needs and assets assessment was …


Label-Free Evaluation Of Mouse Embryo Quality Using Time-Lapse Bright Field And Optical Coherence Microscopy, Fei Wang, Senyue Hao, Kibeom Park, Ali Ahmady, Chao Zhou Apr 2025

Label-Free Evaluation Of Mouse Embryo Quality Using Time-Lapse Bright Field And Optical Coherence Microscopy, Fei Wang, Senyue Hao, Kibeom Park, Ali Ahmady, Chao Zhou

2020-Current year OA Pubs

The selection of high-quality embryos is essential to enhance the implantation rate for in vitro fertilization (IVF). Optical coherence microscopy (OCM) can noninvasively provide three-dimensional (3D) high-resolution imaging of developing embryos. The revealed microstructures can be used for accurate embryo evaluation. Here, we acquire time-lapse 3D OCM images with co-registered bright-field imaging on mouse embryo development from the one-cell stage to the fully hatched blastocyst inside an incubator. Our results demonstrate the capability of OCM to detect structural features of the developing embryos. The second and third embryonic cell cycles are indicated to be associated with blastocyst formation and the …


Atm-Dependent Dna Damage Response Constrains Cell Growth And Drives Clonal Hematopoiesis In Telomere Biology Disorders, Christopher M. Sande, Karolyn A. Oetjen, Daniel C. Link, Andrew E. Gelman, Laneshia K. Tague, Et Al. Apr 2025

Atm-Dependent Dna Damage Response Constrains Cell Growth And Drives Clonal Hematopoiesis In Telomere Biology Disorders, Christopher M. Sande, Karolyn A. Oetjen, Daniel C. Link, Andrew E. Gelman, Laneshia K. Tague, Et Al.

2020-Current year OA Pubs

Telomere biology disorders (TBDs) are genetic diseases caused by defective telomere maintenance. TBD patients often develop bone marrow failure and have an increased risk of myeloid neoplasms. To better understand the factors underlying hematopoietic outcomes in TBD, we comprehensively evaluated acquired genetic alterations in hematopoietic cells from 166 pediatric and adult TBD patients. Of these patients, 47.6% (28.8% of children, 56.1% of adults) had clonal hematopoiesis. Recurrent somatic alterations involved telomere maintenance genes (7.6%), spliceosome genes (10.4%, mainly U2AF1 p.S34), and chromosomal alterations (20.2%), including 1q gain (5.9%). Somatic variants affecting the DNA damage response (DDR) were identified in 21.5% …