Open Access. Powered by Scholars. Published by Universities.®

Medicine and Health Sciences Commons™

Open Access. Powered by Scholars. Published by Universities.®

Articles 5821 - 5850 of 7291

Full-Text Articles in Medicine and Health Sciences

First-In-Human Phase I/Ii Iconic Trial Of The Icos Agonist Vopratelimab Alone And With Nivolumab: Icos-High Cd4 T-Cell Populations And Predictors Of Response, Timothy A Yap, Russell K Pachynski, Haeseong Park, Et Al Sep 2022

First-In-Human Phase I/Ii Iconic Trial Of The Icos Agonist Vopratelimab Alone And With Nivolumab: Icos-High Cd4 T-Cell Populations And Predictors Of Response, Timothy A Yap, Russell K Pachynski, Haeseong Park, Et Al

2020-Current year OA Pubs

PURPOSE: The first-in-human phase I/II ICONIC trial evaluated an investigational inducible costimulator (ICOS) agonist, vopratelimab, alone and in combination with nivolumab in patients with advanced solid tumors.

PATIENTS AND METHODS: In phase I, patients were treated with escalating doses of intravenous vopratelimab alone or with nivolumab. Primary objectives were safety, tolerability, MTD, and recommended phase II dose (RP2D). Phase II enriched for ICOS-positive (ICOS+) tumors; patients were treated with vopratelimab at the monotherapy RP2D alone or with nivolumab. Pharmacokinetics, pharmacodynamics, and predictive biomarkers of response to vopratelimab were assessed.

RESULTS: ICONIC enrolled 201 patients. Vopratelimab alone and with nivolumab was …


Coronavirus Disease 2019 (Covid-19) Vaccination Preparedness Policies In Us Hospitals, Susan E Beekmann, Hilary M Babcock, Mark S Rasnake, Thomas R Talbot, Philip M Polgreen Sep 2022

Coronavirus Disease 2019 (Covid-19) Vaccination Preparedness Policies In Us Hospitals, Susan E Beekmann, Hilary M Babcock, Mark S Rasnake, Thomas R Talbot, Philip M Polgreen

2020-Current year OA Pubs

We surveyed infectious disease specialists about early coronavirus disease 2019 (COVID-19) vaccination preparedness. Almost all responding institutions rated their facility's preparedness plan as either excellent or adequate. Vaccine hesitancy and concern about adverse reactions were the most commonly anticipated barriers to COVID-19 vaccination. Only 60% believed that COVID-19 vaccination should be mandatory.


Disease Burden Affects Aging Brain Function, Lori L Beason-Held, Danielle Fournier, Andrea T Shafer, Elisa Fabbri, Yang An, Chiung-Wei Huang, Murat Bilgel, Dean F Wong, Luigi Ferrucci, Susan M Resnick Sep 2022

Disease Burden Affects Aging Brain Function, Lori L Beason-Held, Danielle Fournier, Andrea T Shafer, Elisa Fabbri, Yang An, Chiung-Wei Huang, Murat Bilgel, Dean F Wong, Luigi Ferrucci, Susan M Resnick

2020-Current year OA Pubs

BACKGROUND: Most older adults live with multiple chronic disease conditions, yet the effect of multiple diseases on brain function remains unclear.

METHODS: We examine the relationship between disease multimorbidity and brain activity using regional cerebral blood flow (rCBF) 15O-water PET scans from 97 cognitively normal participants (mean baseline age 76.5) in the Baltimore Longitudinal Study of Aging (BLSA). Multimorbidity index scores, generated from the presence of 13 health conditions, were correlated with PET data at baseline and in longitudinal change (n = 74) over 5.05 (2.74 SD) years.

RESULTS: At baseline, voxel-based analysis showed that higher multimorbidity scores were associated …


An Evaluation Of Patient-Reported Outcomes In Sickle Cell Disease Within A Conceptual Model., Marsha J Treadwell, Swapandeep Mushiana, Sherif M Badawy, Liliana Preiss, Allison A King, Barbara Kroner, Yumei Chen, Jeffrey Glassberg, Victor Gordeuk, Nirmish Shah, Angela Snyder, Theodore Wun, Sickle Cell Disease Implementation Consortium (Scdic) Sep 2022

An Evaluation Of Patient-Reported Outcomes In Sickle Cell Disease Within A Conceptual Model., Marsha J Treadwell, Swapandeep Mushiana, Sherif M Badawy, Liliana Preiss, Allison A King, Barbara Kroner, Yumei Chen, Jeffrey Glassberg, Victor Gordeuk, Nirmish Shah, Angela Snyder, Theodore Wun, Sickle Cell Disease Implementation Consortium (Scdic)

2020-Current year OA Pubs

PURPOSE: To examine the relations between patient-reported outcomes (PROs) within a conceptual model for adults with sickle cell disease (SCD) ages 18 - 45 years enrolled in the multi-site Sickle Cell Disease Implementation Consortium (SCDIC) registry. We hypothesized that patient and SCD-related factors, particularly pain, and barriers to care would independently contribute to functioning as measured using PRO domains.

METHODS: Participants (N = 2054) completed a 48-item survey including socio-demographics and PRO measures, e.g., social functioning, pain impact, emotional distress, and cognitive functioning. Participants reported on lifetime SCD complications, pain episode frequency and severity, and barriers to healthcare.

RESULTS: Higher …


Risk Factors For Shoulder Disorders Among French Workers: Prospective Cohort Study, Julie Bodin, Ronan Garlantézec, Alexis Descatha, Bradley Evanoff, Thierry Thomas, Yves Roquelaure Sep 2022

Risk Factors For Shoulder Disorders Among French Workers: Prospective Cohort Study, Julie Bodin, Ronan Garlantézec, Alexis Descatha, Bradley Evanoff, Thierry Thomas, Yves Roquelaure

2020-Current year OA Pubs

OBJECTIVES: Shoulder disorders are common in the working population. This longitudinal study aimed to explore the relationships between personal factors and occupational organisational, psychosocial, and biomechanical factors and the incidence of shoulder disorders.

METHODS: A total of 3710 workers in the Pays de la Loire region (Loire Valley area, France) were randomly included by their occupational physician in the Cosali cohort between 2002 and 2005. All workers completed a self-administered questionnaire about personal factors and work exposure, and using a standardised physical examination, occupational physicians diagnosed shoulder disorders. Between 2007 and 2010, 1611 workers were re-examined by their occupational physician. …


A Narrative Review Of Irritable Bowel Syndrome With Diarrhea: A Primer For Primary Care Providers, Baha Moshiree, Joel J Heidelbaugh, Gregory S Sayuk Sep 2022

A Narrative Review Of Irritable Bowel Syndrome With Diarrhea: A Primer For Primary Care Providers, Baha Moshiree, Joel J Heidelbaugh, Gregory S Sayuk

2020-Current year OA Pubs

Irritable bowel syndrome with diarrhea (IBS-D) is a chronic disorder of gut-brain interaction, characterized by recurrent abdominal pain in association with more frequent, loose stools. The pathophysiology of irritable bowel syndrome (IBS) includes disordered gut motility, alterations in gut microbiota, neural-hormonal system abnormalities, immune reactivity, and visceral hypersensitivity. Timely diagnosis of IBS-D can be achieved easily using clinical criteria. Formal IBS diagnosis is important for optimizing treatment and patient outcomes and facilitating patient access to appropriate educational resources. Yet, given the symptom overlap with other gastrointestinal conditions, diagnosis of IBS-D often is perceived to be challenging. Treatment of IBS includes …


Empirical Transmit Field Bias Correction Of T1w/T2w Myelin Maps, Matthew F. Glasser, Timothy S. Coalson, Michael P. Harms, Junqian Xu, Graham L. Baum, Joonas A. Autio, Edward J. Auerbach, Douglas N. Greve, Essa Yacoub, David C. Van Essen, Nicholas A. Bock, Takuya Hayashi Sep 2022

Empirical Transmit Field Bias Correction Of T1w/T2w Myelin Maps, Matthew F. Glasser, Timothy S. Coalson, Michael P. Harms, Junqian Xu, Graham L. Baum, Joonas A. Autio, Edward J. Auerbach, Douglas N. Greve, Essa Yacoub, David C. Van Essen, Nicholas A. Bock, Takuya Hayashi

2020-Current year OA Pubs

T1-weighted divided by T2-weighted (T1w/T2w) myelin maps were initially developed for neuroanatomical analyses such as identifying cortical areas, but they are increasingly used in statistical comparisons across individuals and groups with other variables of interest. Existing T1w/T2w myelin maps contain radiofrequency transmit field (B1+) biases, which may be correlated with these variables of interest, leading to potentially spurious results. Here we propose two empirical methods for correcting these transmit field biases using either explicit measures of the transmit field or alternatively a 'pseudo-transmit' approach that is highly correlated with the transmit field at 3T. We find that the resulting corrected …


Clinical Trial Data Of Anti-Pd-1/Pd-L1 Therapy For Recurrent Or Metastatic Nasopharyngeal Carcinoma: A Review, Douglas R Adkins, Robert I. Haddad Sep 2022

Clinical Trial Data Of Anti-Pd-1/Pd-L1 Therapy For Recurrent Or Metastatic Nasopharyngeal Carcinoma: A Review, Douglas R Adkins, Robert I. Haddad

2020-Current year OA Pubs

IMPORTANCE: Anti-programmed cell death receptor-1 (PD-1) therapy is standard of care for incurable recurrent or metastatic non-nasopharyngeal head and neck cancer. In contrast, there are no regulatory agency-approved anti-PD-1 agents indicated for the treatment of recurrent or metastatic nasopharyngeal carcinomas (RM-NPC) in the Western hemisphere, and no standard treatment option exists beyond first-line chemotherapy for RM-NPC. The pace of development of novel systemic therapy regimens for RM-NPC has been slow compared to many other advanced tumor types, leaving an unmet clinical need for these patients with a poor prognosis.

OBSERVATIONS: Recent clinical trials have documented the clinical activity of anti-PD-1 …


High-Coverage Whole-Genome Sequencing Of The Expanded 1000 Genomes Project Cohort Including 602 Trios, Marta Byrska-Bishop, Haley J Abel, Allison A Regier, Ira M Hall, Et Al. Sep 2022

High-Coverage Whole-Genome Sequencing Of The Expanded 1000 Genomes Project Cohort Including 602 Trios, Marta Byrska-Bishop, Haley J Abel, Allison A Regier, Ira M Hall, Et Al.

2020-Current year OA Pubs

The 1000 Genomes Project (1kGP) is the largest fully open resource of whole-genome sequencing (WGS) data consented for public distribution without access or use restrictions. The final, phase 3 release of the 1kGP included 2,504 unrelated samples from 26 populations and was based primarily on low-coverage WGS. Here, we present a high-coverage 3,202-sample WGS 1kGP resource, which now includes 602 complete trios, sequenced to a depth of 30X using Illumina. We performed single-nucleotide variant (SNV) and short insertion and deletion (INDEL) discovery and generated a comprehensive set of structural variants (SVs) by integrating multiple analytic methods through a machine learning …


Adolescent And Young Adult Preferences For Financial Incentives To Support Adherence To Antiretroviral Therapy In Kenya: A Mixed Methods Study, Ingrid Eshun-Wilson, Eliud Akama, Fridah Adhiambo, Zachary Kwena, Bertha Oketch, Sarah Obatsa, Sarah Iguna, Jayne L Kulzer, James Nyanga, Everlyne Nyandieka, Ally Scheve, Elvin H Geng, Elizabeth A Bukusi, Lisa Abuogi Sep 2022

Adolescent And Young Adult Preferences For Financial Incentives To Support Adherence To Antiretroviral Therapy In Kenya: A Mixed Methods Study, Ingrid Eshun-Wilson, Eliud Akama, Fridah Adhiambo, Zachary Kwena, Bertha Oketch, Sarah Obatsa, Sarah Iguna, Jayne L Kulzer, James Nyanga, Everlyne Nyandieka, Ally Scheve, Elvin H Geng, Elizabeth A Bukusi, Lisa Abuogi

2020-Current year OA Pubs

INTRODUCTION: To develop a patient-centred financial incentive delivery strategy to improve antiretroviral treatment adherence in adolescents and young adults (AYA) living with HIV in Kisumu, Kenya, we conducted a mixed methods study exploring preferences.

METHODS: A discrete choice experiment (DCE) and focus group discussion (FGD) were conducted simultaneously to identify preferences for five incentive delivery strategy features: value, eligibility, recipient, format and disbursement frequency. We used consecutive sampling to recruit AYA (14-24 years) living with HIV attending three health facilities in Kisumu, Kenya. We calculated mean preferences, willingness to trade, latent class membership and predictors of latent class membership. The …


An Ips-Derived In Vitro Model Of Human Atrial Conduction, Sherri M Biendarra-Tiegs, Sergey Yechikov, Bhupinder Shergill, Brittany Brumback, Kentaro Takahashi, Venktesh S Shirure, Ruth Estelle Gonzalez, Laura Houshmand, Denise Zhong, Kuo-Chan Weng, Jon Silva, Timothy W Smith, Stacey L Rentschler, Steven C George Sep 2022

An Ips-Derived In Vitro Model Of Human Atrial Conduction, Sherri M Biendarra-Tiegs, Sergey Yechikov, Bhupinder Shergill, Brittany Brumback, Kentaro Takahashi, Venktesh S Shirure, Ruth Estelle Gonzalez, Laura Houshmand, Denise Zhong, Kuo-Chan Weng, Jon Silva, Timothy W Smith, Stacey L Rentschler, Steven C George

2020-Current year OA Pubs

Atrial fibrillation (AF) is the most common arrhythmia in the United States, affecting approximately 1 in 10 adults, and its prevalence is expected to rise as the population ages. Treatment options for AF are limited; moreover, the development of new treatments is hindered by limited (1) knowledge regarding human atrial electrophysiological endpoints (e.g., conduction velocity [CV]) and (2) accurate experimental models. Here, we measured the CV and refractory period, and subsequently calculated the conduction wavelength, in vivo (four subjects with AF and four controls), and ex vivo (atrial slices from human hearts). Then, we created an in vitro model of …


Proteomic Identification Of Potential Target Proteins Of Cathepsin W For Its Development As A Drug Target For Influenza, Sira C Günther, Carles Martínez-Romero, Milagros Sempere Borau, Christine T N Pham, Adolfo García-Sastre, Silke Stertz Aug 2022

Proteomic Identification Of Potential Target Proteins Of Cathepsin W For Its Development As A Drug Target For Influenza, Sira C Günther, Carles Martínez-Romero, Milagros Sempere Borau, Christine T N Pham, Adolfo García-Sastre, Silke Stertz

2020-Current year OA Pubs

Influenza A virus (IAV) coopts numerous host factors for efficient replication. The cysteine protease cathepsin W (CTSW) has been identified as one host factor required for IAV entry, specifically for the escape of IAVs from late endosomes. However, the substrate specificity of CTSW and the proviral mechanism are thus far unknown. Here, we show that intracellular but not secreted CTSW promotes viral entry. We reveal 79 potential direct and 31 potential indirect cellular target proteins of CTSW using the high-throughput proteomic approach terminal amine isotopic labeling of substrates (TAILS) and determine the cleavage motif shared by the substrates of CTSW. …


Evolution Of Multiple Domains Of The Hiv-1 Envelope Glycoprotein During Coreceptor Switch With Ccr5 Antagonist Therapy, Yueqi Du, Ellen Wu, Xiang Gao, Jie Zhang, John C Martin, Bruce A Rosa, Makedonka Mitreva, Lee Ratner Aug 2022

Evolution Of Multiple Domains Of The Hiv-1 Envelope Glycoprotein During Coreceptor Switch With Ccr5 Antagonist Therapy, Yueqi Du, Ellen Wu, Xiang Gao, Jie Zhang, John C Martin, Bruce A Rosa, Makedonka Mitreva, Lee Ratner

2020-Current year OA Pubs

HIV-1 uses CD4 as a receptor and chemokine receptors CCR5 and/or CXCR4 as coreceptors. CCR5 antagonists are a class of antiretrovirals used to inhibit viral entry. Phenotypic prediction algorithms such as Geno2Pheno are used to assess CCR5 antagonist eligibility, for which the V3 region is screened. However, there exist scenarios where the algorithm cannot give an accurate prediction of tropism. The current study examined coreceptor shift of HIV-1 from CCR5-tropic strains to CXCR4-tropic or dual-tropic strains among five subjects in a clinical trial of the CCR5 antagonist vicriviroc. Envelope gene amplicon libraries were constructed and subjected to next-generation sequencing, as …


Membrane Integrity Contributes To Resistance Of Cryptococcus Neoformans To The Cell Wall Inhibitor Caspofungin, Brenda Moreira-Walsh, Abigail Ragsdale, Woei Lam, Rajendra Upadhya, Evan Xu, Jennifer K Lodge, Maureen J Donlin Aug 2022

Membrane Integrity Contributes To Resistance Of Cryptococcus Neoformans To The Cell Wall Inhibitor Caspofungin, Brenda Moreira-Walsh, Abigail Ragsdale, Woei Lam, Rajendra Upadhya, Evan Xu, Jennifer K Lodge, Maureen J Donlin

2020-Current year OA Pubs

The fungal pathogen Cryptococcus neoformans causes up to 278 000 infections each year globally, resulting in up to 180,000 deaths annually, mostly impacting immunocompromised people. Therapeutic options for C. neoformans infections are very limited. Caspofungin, a member of the echinocandin class of antifungals, is generally well tolerated but clinically ineffective against C. neoformans. We sought to identify biological processes that can be targeted to render the cell more susceptible to echinocandins by screening the available libraries of gene deletion mutants made in the KN99α background for caspofungin sensitivity. We adapted a Candida albicans fungal biofilm assay for the growth characteristics …


Optimal Urine Culture Diagnostic Stewardship Practice- Results From An Expert Modified-Delphi Procedure, Kimberly C Claeys, Stephen Y Liang, Et Al. Aug 2022

Optimal Urine Culture Diagnostic Stewardship Practice- Results From An Expert Modified-Delphi Procedure, Kimberly C Claeys, Stephen Y Liang, Et Al.

2020-Current year OA Pubs

BACKGROUND: Urine cultures are nonspecific and often lead to misdiagnosis of urinary tract infection and unnecessary antibiotics. Diagnostic stewardship is a set of procedures that modifies test ordering, processing, and reporting in order to optimize diagnosis and downstream treatment. In this study, we aimed to develop expert guidance on best practices for urine culture diagnostic stewardship.

METHODS: A RAND-modified Delphi approach with a multidisciplinary expert panel was used to ascertain diagnostic stewardship best practices. Clinical questions to guide recommendations were grouped into three thematic areas (ordering, processing, reporting) in practice settings of emergency department, inpatient, ambulatory, and long-term care. Fifteen …


A Multitrait Locus Regulates Sarbecovirus Pathogenesis, Alexandra Schäfer, Emma S Winkler, Michael S Diamond, Et Al Aug 2022

A Multitrait Locus Regulates Sarbecovirus Pathogenesis, Alexandra Schäfer, Emma S Winkler, Michael S Diamond, Et Al

2020-Current year OA Pubs

Infectious diseases have shaped the human population genetic structure, and genetic variation influences the susceptibility to many viral diseases. However, a variety of challenges have made the implementation of traditional human Genome-wide Association Studies (GWAS) approaches to study these infectious outcomes challenging. In contrast, mouse models of infectious diseases provide an experimental control and precision, which facilitates analyses and mechanistic studies of the role of genetic variation on infection. Here we use a genetic mapping cross between two distinct Collaborative Cross mouse strains with respect to severe acute respiratory syndrome coronavirus (SARS-CoV) disease outcomes. We find several loci control differential …


A Pilot Randomized Trial To Examine Effects Of A Hybrid Closed-Loop Insulin Delivery System On Neurodevelopmental And Cognitive Outcomes In Adolescents With Type 1 Diabetes, Allan L Reiss, Ana Maria Arbelaez, Et Al Aug 2022

A Pilot Randomized Trial To Examine Effects Of A Hybrid Closed-Loop Insulin Delivery System On Neurodevelopmental And Cognitive Outcomes In Adolescents With Type 1 Diabetes, Allan L Reiss, Ana Maria Arbelaez, Et Al

2020-Current year OA Pubs

Type 1 diabetes (T1D) is associated with lower scores on tests of cognitive and neuropsychological function and alterations in brain structure and function in children. This proof-of-concept pilot study (ClinicalTrials.gov Identifier NCT03428932) examined whether MRI-derived indices of brain development and function and standardized IQ scores in adolescents with T1D could be improved with better diabetes control using a hybrid closed-loop insulin delivery system. Eligibility criteria for participation in the study included age between 14 and 17 years and a diagnosis of T1D before 8 years of age. Randomization to either a hybrid closed-loop or standard diabetes care group was performed …


Re-Examining Rotavirus Innate Immune Evasion: Potential Applications Of The Reverse Genetics System, Avan Antia, Amanda N Pinski, Siyuan Ding Aug 2022

Re-Examining Rotavirus Innate Immune Evasion: Potential Applications Of The Reverse Genetics System, Avan Antia, Amanda N Pinski, Siyuan Ding

2020-Current year OA Pubs

Rotaviruses represent one of the most successful pathogens in the world, with high infectivity and efficient transmission between the young of many animal species, including humans. To overcome host defenses, rotaviruses have evolved a plethora of strategies to effectively evade the innate immune response, establish initial infection in the small intestine, produce progeny, and shed into the environment. Previously, studying the roles and relative contributions of specific rotaviral factors in innate immune evasion had been challenging without a plasmid-only reverse genetics system. Although still in its infancy, current reverse genetics technology will help address important research questions regarding rotavirus innate …


Distinct Sensitivities To Sars-Cov-2 Variants In Vaccinated Humans And Mice, Alexandra C Walls, Laura A Vanblargan, Michael S Diamond, Et Al. Aug 2022

Distinct Sensitivities To Sars-Cov-2 Variants In Vaccinated Humans And Mice, Alexandra C Walls, Laura A Vanblargan, Michael S Diamond, Et Al.

2020-Current year OA Pubs

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 has led to the development of a large number of vaccines, several of which are now approved for use in humans. Understanding vaccine-elicited antibody responses against emerging SARS-CoV-2 variants of concern (VOCs) in real time is key to inform public health policies. Serum neutralizing antibody titers are the current best correlate of protection from SARS-CoV-2 challenge in non-human primates and a key metric to understand immune evasion of VOCs. We report that vaccinated BALB/c mice do not recapitulate faithfully the breadth and potency of neutralizing antibody responses elicited …


Blocking Chop-Dependent Txnip Shuttling To Mitochondria Attenuates Albuminuria And Mitigates Kidney Injury In Nephrotic Syndrome, Sun-Ji Park, Yeawon Kim, Chuang Li, Junwoo Suh, Jothilingam Sivapackiam, Tassia M Goncalves, George Jarad, Guoyan Zhao, Fumihiko Urano, Vijay Sharma, Ying Maggie Chen Aug 2022

Blocking Chop-Dependent Txnip Shuttling To Mitochondria Attenuates Albuminuria And Mitigates Kidney Injury In Nephrotic Syndrome, Sun-Ji Park, Yeawon Kim, Chuang Li, Junwoo Suh, Jothilingam Sivapackiam, Tassia M Goncalves, George Jarad, Guoyan Zhao, Fumihiko Urano, Vijay Sharma, Ying Maggie Chen

2020-Current year OA Pubs

Albuminuria is a hallmark of glomerular disease of various etiologies. It is not only a symptom of glomerular disease but also a cause leading to glomerulosclerosis, interstitial fibrosis, and eventually, a decline in kidney function. The molecular mechanism underlying albuminuria-induced kidney injury remains poorly defined. In our genetic model of nephrotic syndrome (NS), we have identified CHOP (C/EBP homologous protein)-TXNIP (thioredoxin-interacting protein) as critical molecular linkers between albuminuria-induced ER dysfunction and mitochondria dyshomeostasis. TXNIP is a ubiquitously expressed redox protein that binds to and inhibits antioxidant enzyme, cytosolic thioredoxin 1 (Trx1), and mitochondrial Trx2. However, very little is known about …


N1-Methylpseudouridine Found Within Covid-19 Mrna Vaccines Produces Faithful Protein Products, Kyusik Q Kim, Bhagyashri D Burgute, Shin-Cheng Tzeng, Crystal Jing, Courtney Jungers, Junya Zhang, Liewei L Yan, Richard D Vierstra, Sergej Djuranovic, Bradley S Evans, Hani S Zaher Aug 2022

N1-Methylpseudouridine Found Within Covid-19 Mrna Vaccines Produces Faithful Protein Products, Kyusik Q Kim, Bhagyashri D Burgute, Shin-Cheng Tzeng, Crystal Jing, Courtney Jungers, Junya Zhang, Liewei L Yan, Richard D Vierstra, Sergej Djuranovic, Bradley S Evans, Hani S Zaher

2020-Current year OA Pubs

Synthetic mRNA technology is a promising avenue for treating and preventing disease. Key to the technology is the incorporation of modified nucleotides such as N1-methylpseudouridine (m1Ψ) to decrease immunogenicity of the RNA. However, relatively few studies have addressed the effects of modified nucleotides on the decoding process. Here, we investigate the effect of m1Ψ and the related modification pseudouridine (Ψ) on translation. In a reconstituted system, we find that m1Ψ does not significantly alter decoding accuracy. More importantly, we do not detect an increase in miscoded peptides when mRNA containing m1Ψ is translated in cell culture, compared with unmodified mRNA. …


Spatiotemporal Correlation Analysis Of Hydraulic Fracturing And Stroke In The United States, Chuanbo Hu, Bin Liu, Shuo Wang, Zhenduo Zhu, Amelia Adcock, James Simpkins, Xin Li Aug 2022

Spatiotemporal Correlation Analysis Of Hydraulic Fracturing And Stroke In The United States, Chuanbo Hu, Bin Liu, Shuo Wang, Zhenduo Zhu, Amelia Adcock, James Simpkins, Xin Li

2020-Current year OA Pubs

Hydraulic fracturing or fracking has led to a rapid growth of oil and gas production in the United States, but the impact of fracking on public health is an important but underresearched topic. We designed a methodology to study spatiotemporal correlations between the risk of fracking and stroke mortality. An annualized loss expectancy (ALE) model is applied to quantify the risk of fracking. The geographically and temporally weighted regression (GTWR) model is used to analyze spatiotemporal correlations of stroke mortality, fracking ALE, and nine other socioeconomic- and health-related factors. The analysis shows that fracking ALE is moderately correlated with stroke …


Comparative Risks Of Initial Aortic Events Associated With Genetic Thoracic Aortic Disease, Ellen S. Regalado, Alan C. Braverman, Et Al. Aug 2022

Comparative Risks Of Initial Aortic Events Associated With Genetic Thoracic Aortic Disease, Ellen S. Regalado, Alan C. Braverman, Et Al.

2020-Current year OA Pubs

BACKGROUND: Pathogenic variants in 11 genes predispose individuals to heritable thoracic aortic disease (HTAD), but limited data are available to stratify the risk for aortic events associated with these genes.

OBJECTIVES: This study sought to compare the risk of first aortic event, specifically thoracic aortic aneurysm surgery or an aortic dissection, among 7 HTAD genes and variant types within each gene.

METHODS: A retrospective cohort of probands and relatives with rare variants in 7 genes for HTAD (n = 1,028) was assessed for the risk of first aortic events based on the gene altered, pathogenic variant type, sex, proband status, …


Subcortical-Cortical Dynamical States Of The Human Brain And Their Breakdown In Stroke, Chiara Favaretto, Michele Allegra, Gustavo Deco, Nicholas V Metcalf, Joseph C Griffis, Gordon L Shulman, Andrea Brovelli, Maurizio Corbetta Aug 2022

Subcortical-Cortical Dynamical States Of The Human Brain And Their Breakdown In Stroke, Chiara Favaretto, Michele Allegra, Gustavo Deco, Nicholas V Metcalf, Joseph C Griffis, Gordon L Shulman, Andrea Brovelli, Maurizio Corbetta

2020-Current year OA Pubs

The mechanisms controlling dynamical patterns in spontaneous brain activity are poorly understood. Here, we provide evidence that cortical dynamics in the ultra-slow frequency range (<0.01-0.1 Hz) requires intact cortical-subcortical communication. Using functional magnetic resonance imaging (fMRI) at rest, we identify Dynamic Functional States (DFSs), transient but recurrent clusters of cortical and subcortical regions synchronizing at ultra-slow frequencies. We observe that shifts in cortical clusters are temporally coincident with shifts in subcortical clusters, with cortical regions flexibly synchronizing with either limbic regions (hippocampus/amygdala), or subcortical nuclei (thalamus/basal ganglia). Focal lesions induced by stroke, especially those damaging white matter connections between basal ganglia/thalamus and cortex, provoke anomalies in the fraction times, dwell times, and transitions between DFSs, causing a bias toward abnormal network integration. Dynamical anomalies observed 2 weeks after stroke recover in time and contribute to explaining neurological impairment and long-term outcome.


Apoptosis Detection In Retinal Ganglion Cells Using Quantitative Changes In Multichannel Fluorescence Colocalization, Xudong Qiu, Seth T Gammon, James R Johnson, Federica Pisaneschi, Steven W Millward, Edward M Barnett, David Piwnica-Worms Aug 2022

Apoptosis Detection In Retinal Ganglion Cells Using Quantitative Changes In Multichannel Fluorescence Colocalization, Xudong Qiu, Seth T Gammon, James R Johnson, Federica Pisaneschi, Steven W Millward, Edward M Barnett, David Piwnica-Worms

2020-Current year OA Pubs

KcapTR488 is a dual-fluorophore peptide sensor for the real-time reporting of programmed cell death by fluorescence imaging. KcapTR488 contains a nuclear localization sequence (NLS) conjugated with Texas Red, a caspase-cleavable sequence (DEVD), and a C-terminus conjugated to Alexa Fluor 488 (AF488). The synthesis and preliminary evaluation in cellulo of KcapTR488 for monitoring cell death by fluorescence imaging has been previously reported, but its utility in vivo has yet to be tested or validated. Herein, in vitro solution experiments verified the intramolecular fluorescence resonance energy transfer (FRET) between the two fluorophores and enabled a quantitative analysis of enzyme rates and selectivity. …


Capg Is Required For Ebola Virus Infection By Controlling Virus Egress From Infected Cells, Hiroyuki Mori, James P Connell, Callie J Donahue, Ruthmabel Boytz, Yen Thi Kim Nguyen, Daisy W Leung, Douglas J Lacount, Robert A Davey Aug 2022

Capg Is Required For Ebola Virus Infection By Controlling Virus Egress From Infected Cells, Hiroyuki Mori, James P Connell, Callie J Donahue, Ruthmabel Boytz, Yen Thi Kim Nguyen, Daisy W Leung, Douglas J Lacount, Robert A Davey

2020-Current year OA Pubs

The replication of Ebola virus (EBOV) is dependent upon actin functionality, especially at cell entry through macropinocytosis and at release of virus from cells. Previously, major actin-regulatory factors involved in actin nucleation, such as Rac1 and Arp2/3, were shown important in both steps. However, downstream of nucleation, many other cell factors are needed to control actin dynamics. How these regulate EBOV infection remains largely unclear. Here, we identified the actin-regulating protein, CAPG, as important for EBOV replication. Notably, knockdown of CAPG specifically inhibited viral infectivity and yield of infectious particles. Cell-based mechanistic analysis revealed a requirement of CAPG for virus …


Organization Of The Gravity-Sensing System In Zebrafish, Zhikai Liu, David G C Hildebrand, Joshua L Morgan, Yizhen Jia, Nicholas Slimmon, Martha W Bagnall Aug 2022

Organization Of The Gravity-Sensing System In Zebrafish, Zhikai Liu, David G C Hildebrand, Joshua L Morgan, Yizhen Jia, Nicholas Slimmon, Martha W Bagnall

2020-Current year OA Pubs

Motor circuits develop in sequence from those governing fast movements to those governing slow. Here we examine whether upstream sensory circuits are organized by similar principles. Using serial-section electron microscopy in larval zebrafish, we generated a complete map of the gravity-sensing (utricular) system spanning from the inner ear to the brainstem. We find that both sensory tuning and developmental sequence are organizing principles of vestibular topography. Patterned rostrocaudal innervation from hair cells to afferents creates an anatomically inferred directional tuning map in the utricular ganglion, forming segregated pathways for rostral and caudal tilt. Furthermore, the mediolateral axis of the ganglion …


Neurogenetic And Epigenetic Aspects Of Cannabinoids, Catherine A Dennen, Kenneth Blum, Abdalla Bowirrat, Jag Khalsa, Panayotis K Thanos, David Baron, Rajendra D Badgaiyan, Ashim Gupta, Eric R Braverman, Mark S Gold Aug 2022

Neurogenetic And Epigenetic Aspects Of Cannabinoids, Catherine A Dennen, Kenneth Blum, Abdalla Bowirrat, Jag Khalsa, Panayotis K Thanos, David Baron, Rajendra D Badgaiyan, Ashim Gupta, Eric R Braverman, Mark S Gold

2020-Current year OA Pubs

Cannabis is one of the most commonly used and abused illicit drugs in the world today. The United States (US) currently has the highest annual prevalence rate of cannabis consumption in the world, 17.9% in individuals aged 12 or older, and it is on the rise. With increasing cannabis use comes the potential for an increase in abuse, and according to the Substance Abuse and Mental Health Services Administration (SAMHSA), approximately 5.1% of Americans had Cannabis Use Disorder (CUD) in 2020. Research has shown that genetics and epigenetics play a significant role in cannabis use and CUD. In fact, approximately …


Statistical Validation Of Risk Alleles In Genetic Addiction Risk Severity (Gars) Test: Early Identification Of Risk For Alcohol Use Disorder (Aud) In 74,566 Case-Control Subjects, Kenneth Blum, Mark S Gold, Et Al. Aug 2022

Statistical Validation Of Risk Alleles In Genetic Addiction Risk Severity (Gars) Test: Early Identification Of Risk For Alcohol Use Disorder (Aud) In 74,566 Case-Control Subjects, Kenneth Blum, Mark S Gold, Et Al.

2020-Current year OA Pubs

Since 1990, when our laboratory published the association of the DRD2 Taq A1 allele and severe alcoholism in


Modelling Neurological Diseases In Large Animals: Criteria For Model Selection And Clinical Assessment, Samantha L Eaton, Jonathan D Cooper, Et Al. Aug 2022

Modelling Neurological Diseases In Large Animals: Criteria For Model Selection And Clinical Assessment, Samantha L Eaton, Jonathan D Cooper, Et Al.

2020-Current year OA Pubs

No abstract provided.