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The Geriatric Emergency Care Applied Research (Gear) Network Approach: A Protocol To Advance Stakeholder Consensus And Research Priorities In Geriatrics And Dementia Care In The Emergency Department, Ula Hwang, Christopher Carpenter, Scott Dresden, Jeffrey Dussetschleger, Angela Gifford, Ly Hoang, Jesseca Leggett, Armin Nowroozpoor, Zachary Taylor, Manish Shah, The Gear And Gear 2.0 Networks Apr 2022

The Geriatric Emergency Care Applied Research (Gear) Network Approach: A Protocol To Advance Stakeholder Consensus And Research Priorities In Geriatrics And Dementia Care In The Emergency Department, Ula Hwang, Christopher Carpenter, Scott Dresden, Jeffrey Dussetschleger, Angela Gifford, Ly Hoang, Jesseca Leggett, Armin Nowroozpoor, Zachary Taylor, Manish Shah, The Gear And Gear 2.0 Networks

Open Access Publications

INTRODUCTION: Increasingly, older adults are turning to emergency departments (EDs) to address healthcare needs. To achieve these research demands, infrastructure is needed to both generate evidence of intervention impact and advance the development of implementation science, pragmatic trials evaluation and dissemination of findings from studies addressing the emergency care needs of older adults. The Geriatric Emergency Care Applied Research Network (https://gearnetwork.org) has been created in response to these scientific needs-to build a transdisciplinary infrastructure to support the research that will optimise emergency care for older adults and persons living with dementia.

METHODS AND ANALYSIS: In this paper, we describe our …


Applying Systems Thinking To Identify Enablers And Challenges To Scale-Up Interventions For Hypertension And Diabetes In Low-Income And Middle-Income Countries: Protocol For A Longitudinal Mixed-Methods Study, Anusha Ramani-Chander, Mark D Huffman, Et Al Apr 2022

Applying Systems Thinking To Identify Enablers And Challenges To Scale-Up Interventions For Hypertension And Diabetes In Low-Income And Middle-Income Countries: Protocol For A Longitudinal Mixed-Methods Study, Anusha Ramani-Chander, Mark D Huffman, Et Al

Open Access Publications

INTRODUCTION: There is an urgent need to reduce the burden of non-communicable diseases (NCDs), particularly in low-and middle-income countries, where the greatest burden lies. Yet, there is little research concerning the specific issues involved in scaling up NCD interventions targeting low-resource settings. We propose to examine this gap in up to 27 collaborative projects, which were funded by the Global Alliance for Chronic Diseases (GACD) 2019 Scale Up Call, reflecting a total funding investment of approximately US$50 million. These projects represent diverse countries, contexts and adopt varied approaches and study designs to scale-up complex, evidence-based interventions to improve hypertension and …


An International Analysis Evaluating Frontline Bendamustine With Rituximab In Extranodal Marginal Zone Lymphoma, Juan Pablo Alderuccio, Marcus P Watkins, Raya Saba, Brad S Kahl, Et Al Apr 2022

An International Analysis Evaluating Frontline Bendamustine With Rituximab In Extranodal Marginal Zone Lymphoma, Juan Pablo Alderuccio, Marcus P Watkins, Raya Saba, Brad S Kahl, Et Al

Open Access Publications

Extranodal marginal zone lymphoma (EMZL) is a heterogeneous non-Hodgkin lymphoma. No consensus exists regarding the standard-of-care in patients with advanced-stage disease. Current recommendations are largely adapted from follicular lymphoma, for which bendamustine with rituximab (BR) is an established approach. We analyzed the safety and efficacy of frontline BR in EMZL using a large international consortium. We included 237 patients with a median age of 63 years (range, 21-85). Most patients presented with Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 (n = 228; 96.2%), stage III/IV (n = 179; 75.5%), and intermediate (49.8%) or high (33.3%) Mucosa Associated …


Identification Of Small Regions Of Overlap From Copy Number Variable Regions In Patients With Hypospadias, Carter H Scott, Ina E Amarillo Apr 2022

Identification Of Small Regions Of Overlap From Copy Number Variable Regions In Patients With Hypospadias, Carter H Scott, Ina E Amarillo

Open Access Publications

Hypospadias is a common form of congenital atypical sex development that is often associated with other congenital comorbidities. Many genes have been associated with the condition, most commonly single sequence variations. Further investigations of recurrent and overlapping copy number variations (CNVs) have resulted in the identification of genes and chromosome regions associated with various conditions, including differences of sex development (DSD). In this retrospective study, we investigated the DECIPHER database, as well as an internal institutional database, to identify small recurrent CNVs among individuals with isolated and syndromic hypospadias. We further investigated these overlapping recurrent CNVs to identify 75 smallest …


Machine Learning-Based Scoring Models To Predict Hematopoietic Stem Cell Mobilization In Allogeneic Donors, Jingyu Xiang, Min Shi, Mark A Fiala, Feng Gao, Michael P Rettig, Geoffrey L Uy, Mark A Schroeder, Katherine N Weilbaecher, Keith E Stockerl-Goldstein, Shamim Mollah, John F Dipersio Apr 2022

Machine Learning-Based Scoring Models To Predict Hematopoietic Stem Cell Mobilization In Allogeneic Donors, Jingyu Xiang, Min Shi, Mark A Fiala, Feng Gao, Michael P Rettig, Geoffrey L Uy, Mark A Schroeder, Katherine N Weilbaecher, Keith E Stockerl-Goldstein, Shamim Mollah, John F Dipersio

Open Access Publications

Mobilized peripheral blood has become the primary source of hematopoietic stem cells for both autologous and allogeneic stem cell transplantation. Granulocyte colony-stimulating factor (G-CSF) is currently the standard agent used in the allogeneic setting. Despite the high mobilization efficacy in most donors, G-CSF requires 4-5 days of daily administration, and a small percentage of the donors fail to mobilize an optimal number of stem cells necessary for a safe allogeneic stem cell transplant. In this study, we retrospectively reviewed 1361 related allogeneic donors who underwent stem cell mobilization at Washington University. We compared the standard mobilization agent G-CSF with five …


Laser Interstitial Thermal Therapy In Grade 2/3 Idh1/2 Mutant Gliomas: A Preliminary Report And Literature Review, Gabrielle W Johnson, Rowland H Han, Matthew D Smyth, Eric C Leuthardt, Albert H Kim Apr 2022

Laser Interstitial Thermal Therapy In Grade 2/3 Idh1/2 Mutant Gliomas: A Preliminary Report And Literature Review, Gabrielle W Johnson, Rowland H Han, Matthew D Smyth, Eric C Leuthardt, Albert H Kim

Open Access Publications

Laser interstitial thermal therapy (LITT) has become an increasingly utilized alternative to surgical resection for the treatment of glioma in patients. However, treatment outcomes in isocitrate dehydrogenase 1 and 2 (


Connectomic Profiling And Vagus Nerve Stimulation Outcomes Study (Connectivos): A Prospective Observational Protocol To Identify Biomarkers Of Seizure Response In Children And Youth, Lauren Siegel, Matthew D Smyth, Et Al Apr 2022

Connectomic Profiling And Vagus Nerve Stimulation Outcomes Study (Connectivos): A Prospective Observational Protocol To Identify Biomarkers Of Seizure Response In Children And Youth, Lauren Siegel, Matthew D Smyth, Et Al

Open Access Publications

INTRODUCTION: Vagus nerve stimulation (VNS) is a neuromodulation therapy that can reduce the seizure burden of children with medically intractable epilepsy. Despite the widespread use of VNS to treat epilepsy, there are currently no means to preoperatively identify patients who will benefit from treatment. The objective of the present study is to determine clinical and neural network-based correlates of treatment outcome to better identify candidates for VNS therapy.

METHODS AND ANALYSIS: In this multi-institutional North American study, children undergoing VNS and their caregivers will be prospectively recruited. All patients will have documentation of clinical history, physical and neurological examination and …


Combination Of Sulindac And Eflornithine Delays The Need For Lower Gastrointestinal Surgery In Patients With Familial Adenomatous Polyposis: Post Hoc Analysis Of A Randomized Clinical Trial, Francesc Balaguer, Paul E Wise, Et Al Apr 2022

Combination Of Sulindac And Eflornithine Delays The Need For Lower Gastrointestinal Surgery In Patients With Familial Adenomatous Polyposis: Post Hoc Analysis Of A Randomized Clinical Trial, Francesc Balaguer, Paul E Wise, Et Al

Open Access Publications

BACKGROUND: Colectomy and proctocolectomy are the initial standard of care for patients with familial adenomatous polyposis. Pharmacotherapy to prevent the progression of polyposis and surgeries in the lower GI tract would be beneficial to patients with this disease.

OBJECTIVE: This analysis aimed to evaluate the impact of eflornithine-sulindac combination versus monotherapy in delaying time to disease progression in the lower GI tract of patients with familial adenomatous polyposis.

DESIGN: This is a post hoc analysis of a randomized phase 3 trial.

SETTING: This study was conducted in 21 hospitals in 7 countries treating patients with familial adenomatous polyposis.

PATIENTS: Adults …


Vestibular Rehabilitation For Peripheral Vestibular Hypofunction: An Updated Clinical Practice Guideline From The Academy Of Neurologic Physical Therapy Of The American Physical Therapy Association, Courtney D Hall, Joel A Goebel, Et Al Apr 2022

Vestibular Rehabilitation For Peripheral Vestibular Hypofunction: An Updated Clinical Practice Guideline From The Academy Of Neurologic Physical Therapy Of The American Physical Therapy Association, Courtney D Hall, Joel A Goebel, Et Al

Open Access Publications

BACKGROUND: Uncompensated vestibular hypofunction can result in symptoms of dizziness, imbalance, and/or oscillopsia, gaze and gait instability, and impaired navigation and spatial orientation; thus, may negatively impact an individual's quality of life, ability to perform activities of daily living, drive, and work. It is estimated that one-third of adults in the United States have vestibular dysfunction and the incidence increases with age. There is strong evidence supporting vestibular physical therapy for reducing symptoms, improving gaze and postural stability, and improving function in individuals with vestibular hypofunction. The purpose of this revised clinical practice guideline is to improve quality of care …


Global Variation In Studies Of Articular Cartilage Procedures Of The Knee: A Systematic Review, R. Garrett Steinmetz, J. Jared Guth, Matthew J Matava, Matthew V Smith, Robert H Brophy Apr 2022

Global Variation In Studies Of Articular Cartilage Procedures Of The Knee: A Systematic Review, R. Garrett Steinmetz, J. Jared Guth, Matthew J Matava, Matthew V Smith, Robert H Brophy

Open Access Publications

OBJECTIVE: The objective of this study was to determine whether there are significant differences in terms of indications, techniques, patient variables, and objective and subjective outcome scores as a function of the geographic locale of published studies of knee articular cartilage surgery.

METHODS: An electronic database search was performed of clinical studies evaluating knee articular cartilage procedures from 2000 to 2021. Studies were separated into global regions (Europe, Asia, North America, and South America) based on the study country. All cartilage-based treatments in each region were recorded. Patient age and sex, mechanism of injury, cartilage lesion size and location, follow-up …


Current And Future Nonstimulants In The Treatment Of Pediatric Adhd: Monoamine Reuptake Inhibitors, Receptor Modulators, And Multimodal Agents, Andrew J Cutler, Gregory W Mattingly, Rakesh Jain, Welton O'Neal Apr 2022

Current And Future Nonstimulants In The Treatment Of Pediatric Adhd: Monoamine Reuptake Inhibitors, Receptor Modulators, And Multimodal Agents, Andrew J Cutler, Gregory W Mattingly, Rakesh Jain, Welton O'Neal

Open Access Publications

Attention-deficit/hyperactivity disorder (ADHD), the single most common neuropsychiatric disorder with cognitive and behavioral manifestations, often starts in childhood and usually persists into adolescence and adulthood. Rarely seen alone, ADHD is most commonly complicated by other neuropsychiatric disorders that must be factored into any intervention plan to optimally address ADHD symptoms. With more than 30 classical Schedule II (CII) stimulant preparations available for ADHD treatment, only three nonstimulants (atomoxetine and extended-release formulations of clonidine and guanfacine) have been approved by the United States Food and Drug Administration (FDA), all of which focus on modulating the noradrenergic system. Given the heterogeneity and …


Applying Implementation Science To Improve Care For Familial Hypercholesterolemia, Laney K Jones, Ross C Brownson, Marc S Williams Apr 2022

Applying Implementation Science To Improve Care For Familial Hypercholesterolemia, Laney K Jones, Ross C Brownson, Marc S Williams

Open Access Publications

PURPOSE OF REVIEW: Improving care of individuals with familial hypercholesteremia (FH) is reliant on the synthesis of evidence-based guidelines and their subsequent implementation into clinical care. This review describes implementation strategies, defined as methods to improve translation of evidence into FH care, that have been mapped to strategies from the Expert Recommendations for Implementing Change (ERIC) compilation.

RECENT FINDINGS: A search using the term 'familial hypercholesterolemia' returned 1350 articles from November 2018 to July 2021. Among these, there were 153 articles related to improving FH care; 1156 were excluded and the remaining 37 were mapped to the ERIC compilation of …


Dlmm As A Lossless One-Shot Algorithm For Collaborative Multi-Site Distributed Linear Mixed Models, Chongliang Luo, Et Al Mar 2022

Dlmm As A Lossless One-Shot Algorithm For Collaborative Multi-Site Distributed Linear Mixed Models, Chongliang Luo, Et Al

Open Access Publications

Linear mixed models are commonly used in healthcare-based association analyses for analyzing multi-site data with heterogeneous site-specific random effects. Due to regulations for protecting patients' privacy, sensitive individual patient data (IPD) typically cannot be shared across sites. We propose an algorithm for fitting distributed linear mixed models (DLMMs) without sharing IPD across sites. This algorithm achieves results identical to those achieved using pooled IPD from multiple sites (i.e., the same effect size and standard error estimates), hence demonstrating the lossless property. The algorithm requires each site to contribute minimal aggregated data in only one round of communication. We demonstrate the …


Comparison Of Bioelectrical Impedance Analysis With Dxa In Adolescents With Cystic Fibrosis Before And After A Resistance Training Intervention, Clifton J Holmes, Susan B Racette, Leslie Symonds, Ana Maria Arbeláez, Chao Cao, Andrea Granados Mar 2022

Comparison Of Bioelectrical Impedance Analysis With Dxa In Adolescents With Cystic Fibrosis Before And After A Resistance Training Intervention, Clifton J Holmes, Susan B Racette, Leslie Symonds, Ana Maria Arbeláez, Chao Cao, Andrea Granados

Open Access Publications

BACKGROUND: The purpose of this pilot study was to compare body composition metrics obtained by two portable bioelectrical impedance analysis (BIA) devices with dual-energy X-ray absorptiometry (DXA) among adolescents with cystic fibrosis (CF) before and after a resistance exercise training program.

METHODS: Participants with CF were assessed using DXA, single-frequency BIA (SFBIA), and multiple-frequency BIA (MFBIA) to quantify percent body fat (%Fat), fat mass (FM), and fat-free mass (FFM) at baseline and after a home-based resistance training intervention comprised of 36, 1 h sessions completed in 12-14 weeks. Repeated measures analysis of variance, paired samples

RESULTS: Ten participants (15.8 ± …


Genome-Wide Association Studies Of Metabolites In Finnish Men Identify Disease-Relevant Loci, Xianyong Yin, Adam E Locke, Erica Young, Liron Ganel, Indraniel Das, Haley Abel, Nathan O Stitziel, Et Al Mar 2022

Genome-Wide Association Studies Of Metabolites In Finnish Men Identify Disease-Relevant Loci, Xianyong Yin, Adam E Locke, Erica Young, Liron Ganel, Indraniel Das, Haley Abel, Nathan O Stitziel, Et Al

Open Access Publications

Few studies have explored the impact of rare variants (minor allele frequency < 1%) on highly heritable plasma metabolites identified in metabolomic screens. The Finnish population provides an ideal opportunity for such explorations, given the multiple bottlenecks and expansions that have shaped its history, and the enrichment for many otherwise rare alleles that has resulted. Here, we report genetic associations for 1391 plasma metabolites in 6136 men from the late-settlement region of Finland. We identify 303 novel association signals, more than one third at variants rare or enriched in Finns. Many of these signals identify genes not previously implicated in metabolite genome-wide association studies and suggest mechanisms for diseases and disease-related traits.


A Bayesian Network To Predict The Risk Of Post Influenza Vaccination Guillain-Barré Syndrome: Development And Validation Study, Yun Huang, Chongliang Luo, Ying Jiang, Jingcheng Du, Cui Tao, Yong Chen, Yuantao Hao Mar 2022

A Bayesian Network To Predict The Risk Of Post Influenza Vaccination Guillain-Barré Syndrome: Development And Validation Study, Yun Huang, Chongliang Luo, Ying Jiang, Jingcheng Du, Cui Tao, Yong Chen, Yuantao Hao

Open Access Publications

BACKGROUND: Identifying the key factors of Guillain-Barré syndrome (GBS) and predicting its occurrence are vital for improving the prognosis of patients with GBS. However, there are scarcely any publications on a forewarning model of GBS. A Bayesian network (BN) model, which is known to be an accurate, interpretable, and interaction-sensitive graph model in many similar domains, is worth trying in GBS risk prediction.

OBJECTIVE: The aim of this study is to determine the most significant factors of GBS and further develop and validate a BN model for predicting GBS risk.

METHODS: Large-scale influenza vaccine postmarketing surveillance data, including 79,165 US …


Locommotion: A Prospective, Non-Interventional, Multinational Study Of Real-Life Current Standards Of Care In Patients With Relapsed And/Or Refractory Multiple Myeloma, Maria-Victoria Mateos, Katja Weisel, Ravi Vij, Et Al Mar 2022

Locommotion: A Prospective, Non-Interventional, Multinational Study Of Real-Life Current Standards Of Care In Patients With Relapsed And/Or Refractory Multiple Myeloma, Maria-Victoria Mateos, Katja Weisel, Ravi Vij, Et Al

Open Access Publications

Despite treatment advances, patients with multiple myeloma (MM) often progress through standard drug classes including proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and anti-CD38 monoclonal antibodies (mAbs). LocoMMotion (ClinicalTrials.gov identifier: NCT04035226) is the first prospective study of real-life standard of care (SOC) in triple-class exposed (received at least a PI, IMiD, and anti-CD38 mAb) patients with relapsed/refractory MM (RRMM). Patients (N = 248; ECOG performance status of 0-1, ≥3 prior lines of therapy or double refractory to a PI and IMiD) were treated with median 4.0 (range, 1-20) cycles of SOC therapy. Overall response rate was 29.8% (95% CI: 24.2-36.0). Median …


Micrornas In Pulmonary Hypertension, From Pathogenesis To Diagnosis And Treatment, Junhua Xu, John Linneman, Yanfeng Zhong, Haoyang Yin, Qinyi Xia, Kang Kang, Deming Gou Mar 2022

Micrornas In Pulmonary Hypertension, From Pathogenesis To Diagnosis And Treatment, Junhua Xu, John Linneman, Yanfeng Zhong, Haoyang Yin, Qinyi Xia, Kang Kang, Deming Gou

Open Access Publications

Pulmonary hypertension (PH) is a fatal and untreatable disease, ultimately leading to right heart failure and eventually death. microRNAs are small, non-coding endogenous RNA molecules that can regulate gene expression and influence various biological processes. Changes in microRNA expression levels contribute to various cardiovascular disorders, and microRNAs have been shown to play a critical role in PH pathogenesis. In recent years, numerous studies have explored the role of microRNAs in PH, focusing on the expression profiles of microRNAs and their signaling pathways in pulmonary artery smooth muscle cells (PASMCs) or pulmonary artery endothelial cells (PAECs), PH models, and PH patients. …


Facing The Realities Of Pragmatic Design Choices In Environmental Health Studies: Experiences From The Household Air Pollution Intervention Network Trial, William Checkley, Victor G Davila-Roman, Et Al Mar 2022

Facing The Realities Of Pragmatic Design Choices In Environmental Health Studies: Experiences From The Household Air Pollution Intervention Network Trial, William Checkley, Victor G Davila-Roman, Et Al

Open Access Publications

No abstract provided.


Mitochondrial Phenotypes In Genetically Diverse Neurodegenerative Diseases And Their Response To Mitofusin Activation, Xiawei Dang, Emily K Walton, Barbara Zablocka, Robert H Baloh, Michael E Shy, Gerald W Dorn Ii Mar 2022

Mitochondrial Phenotypes In Genetically Diverse Neurodegenerative Diseases And Their Response To Mitofusin Activation, Xiawei Dang, Emily K Walton, Barbara Zablocka, Robert H Baloh, Michael E Shy, Gerald W Dorn Ii

Open Access Publications

Mitochondrial fusion is essential to mitochondrial fitness and cellular health. Neurons of patients with genetic neurodegenerative diseases often exhibit mitochondrial fragmentation, reflecting an imbalance in mitochondrial fusion and fission (mitochondrial dysdynamism). Charcot-Marie-Tooth (CMT) disease type 2A is the prototypical disorder of impaired mitochondrial fusion caused by mutations in the fusion protein mitofusin (MFN)2. Yet, cultured CMT2A patient fibroblast mitochondria are often reported as morphologically normal. Metabolic stress might evoke pathological mitochondrial phenotypes in cultured patient fibroblasts, providing a platform for the pre-clinical individualized evaluation of investigational therapeutics. Here, substitution of galactose for glucose in culture media was used to redirect …


Predicting Mitochondrial Dynamic Behavior In Genetically Defined Neurodegenerative Diseases, Gerald W Dorn Ii, Xiawei Dang Mar 2022

Predicting Mitochondrial Dynamic Behavior In Genetically Defined Neurodegenerative Diseases, Gerald W Dorn Ii, Xiawei Dang

Open Access Publications

Mitochondrial dynamics encompass mitochondrial fusion, fission, and movement. Mitochondrial fission and fusion are seemingly ubiquitous, whereas mitochondrial movement is especially important for organelle transport through neuronal axons. Here, we review the roles of different mitochondrial dynamic processes in mitochondrial quantity and quality control, emphasizing their impact on the neurological system in Charcot-Marie-Tooth disease type 2A, amyotrophic lateral sclerosis, Friedrich's ataxia, dominant optic atrophy, and Alzheimer's, Huntington's, and Parkinson's diseases. In addition to mechanisms and concepts, we explore in detail different technical approaches for measuring mitochondrial dynamic dysfunction in vitro, describe how results from tissue culture studies may be applied to …


Adherence Enables Neisseria Gonorrhoeae To Overcome Zinc Limitation Imposed By Nutritional Immunity Proteins, Jocelyn C Ray, Asya Smirnov, Stavros A Maurakis, Simone A Harrison, Eugene Ke, Walter J Chazin, Cynthia Nau Cornelissen, Alison K Criss Mar 2022

Adherence Enables Neisseria Gonorrhoeae To Overcome Zinc Limitation Imposed By Nutritional Immunity Proteins, Jocelyn C Ray, Asya Smirnov, Stavros A Maurakis, Simone A Harrison, Eugene Ke, Walter J Chazin, Cynthia Nau Cornelissen, Alison K Criss

Open Access Publications

Neisseria gonorrhoeae (Gc) must overcome the limitation of metals such as zinc to colonize mucosal surfaces in its obligate human host. While the zinc-binding nutritional immunity proteins calprotectin (S100A8/A9) and psoriasin (S100A7) are abundant in human cervicovaginal lavage fluid, Gc possesses TonB-dependent transporters TdfH and TdfJ that bind and extract zinc from the human version of these proteins, respectively. Here we investigated the contribution of zinc acquisition to Gc infection of epithelial cells of the female genital tract. We found that TdfH and TdfJ were dispensable for survival of strain FA1090 Gc that was associated with Ect1 human immortalized epithelial …


Principles And Applications Of Crispr Toolkit In Virus Manipulation, Diagnosis, And Virus-Host Interactions, Saleh Jamehdor, Sara Pajouhanfar, Sadaf Saba, Georges Uzan, Ali Teimoori, Sina Naserian Mar 2022

Principles And Applications Of Crispr Toolkit In Virus Manipulation, Diagnosis, And Virus-Host Interactions, Saleh Jamehdor, Sara Pajouhanfar, Sadaf Saba, Georges Uzan, Ali Teimoori, Sina Naserian

Open Access Publications

Viruses are one of the most important concerns for human health, and overcoming viral infections is a worldwide challenge. However, researchers have been trying to manipulate viral genomes to overcome various disorders, including cancer, for vaccine development purposes. CRISPR (clustered regularly interspaced short palindromic repeats) is becoming one of the most functional and widely used tools for RNA and DNA manipulation in multiple organisms. This approach has provided an unprecedented opportunity for creating simple, inexpensive, specific, targeted, accurate, and practical manipulations of viruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human immunodeficiency virus-1 (HIV-1), and vaccinia virus. Furthermore, …


Feasibility And Efficacy Of Telehealth-Based Resistance Exercise Training In Adolescents With Cystic Fibrosis And Glucose Intolerance, Clifton J Holmes, Susan B Racette, Leslie Symonds, Ana Maria Arbeláez, Chao Cao, Andrea Granados Mar 2022

Feasibility And Efficacy Of Telehealth-Based Resistance Exercise Training In Adolescents With Cystic Fibrosis And Glucose Intolerance, Clifton J Holmes, Susan B Racette, Leslie Symonds, Ana Maria Arbeláez, Chao Cao, Andrea Granados

Open Access Publications

The aims of this study were to (1) determine the feasibility of a home-based resistance exercise training (RET) program in patients with cystic fibrosis and impaired glucose tolerance using virtual personal training and (2) observe the effects completion of the RET program had on glucose metabolism, pulmonary function, body composition, and physical fitness. The feasibility of the program was defined as 80% compliance. Ten participants (15.80 ± 2.20 yr, 25.1 ± 7.4 kg/m


Exploiting Radiation Induction Of Antigens In Cancer: Targeted Drug Delivery, Vaishali Kapoor, Abhay K Singh, Calvin D Lewis, Sapna Deore, Dennis E Hallahan Mar 2022

Exploiting Radiation Induction Of Antigens In Cancer: Targeted Drug Delivery, Vaishali Kapoor, Abhay K Singh, Calvin D Lewis, Sapna Deore, Dennis E Hallahan

Open Access Publications

Therapeutic antibodies used to treat cancer are effective in patients with advanced-stage disease. For example, antibodies that activate T-lymphocytes improve survival in many cancer subtypes. In addition, antibody-drug conjugates effectively target cytotoxic agents that are specific to cancer. This review discusses radiation-inducible antigens, which are stress-regulated proteins that are over-expressed in cancer. These inducible cell surface proteins become accessible to antibody binding during the cellular response to genotoxic stress. The lead antigens are induced in all histologic subtypes and nearly all advanced-stage cancers, but show little to no expression in normal tissues. Inducible antigens are exploited by using therapeutic antibodies …


Clinical Severity Of, And Effectiveness Of Mrna Vaccines Against, Covid-19 From Omicron, Delta, And Alpha Sars-Cov-2 Variants In The United States: Prospective Observational Study, Adam S Lauring, Hilary M Babcock, Jennie H Kwon, Et Al Mar 2022

Clinical Severity Of, And Effectiveness Of Mrna Vaccines Against, Covid-19 From Omicron, Delta, And Alpha Sars-Cov-2 Variants In The United States: Prospective Observational Study, Adam S Lauring, Hilary M Babcock, Jennie H Kwon, Et Al

Open Access Publications

OBJECTIVES: To characterize the clinical severity of covid-19 associated with the alpha, delta, and omicron SARS-CoV-2 variants among adults admitted to hospital and to compare the effectiveness of mRNA vaccines to prevent hospital admissions related to each variant.

DESIGN: Case-control study.

SETTING: 21 hospitals across the United States.

PARTICIPANTS: 11 690 adults (≥18 years) admitted to hospital: 5728 with covid-19 (cases) and 5962 without covid-19 (controls). Patients were classified into SARS-CoV-2 variant groups based on viral whole genome sequencing, and, if sequencing did not reveal a lineage, by the predominant circulating variant at the time of hospital admission: alpha (11 …


Dose-Finding Study Of Ibrutinib And Venetoclax In Relapsed Or Refractory Mantle Cell Lymphoma, Craig A Portell, Nolan A Wages, Brad S Kahl, Lihua E Budde, Robert W Chen, Jonathon B Cohen, Nikole E Varhegyi, Gina R Petroni, Michael E Williams Mar 2022

Dose-Finding Study Of Ibrutinib And Venetoclax In Relapsed Or Refractory Mantle Cell Lymphoma, Craig A Portell, Nolan A Wages, Brad S Kahl, Lihua E Budde, Robert W Chen, Jonathon B Cohen, Nikole E Varhegyi, Gina R Petroni, Michael E Williams

Open Access Publications

Relapsed Mantle cell lymphoma (MCL) is often treated with Bruton's tyrosine kinase inhibitors (BTKi); however, post-BTKi relapse can be challenging. Adding venetoclax (VEN) to ibrutinib (IBR) has shown synergy in preclinical MCL models. Prior MCL studies of the combination show promising efficacy but have conducted limited dose finding. We sought to identify the optimal dosing combination, based on efficacy and toxicity, utilizing a continual reassessment method of 6 combinations of IBR (280 mg, 420 mg, and 560 mg by mouth daily) and VEN (max dose of 200 mg and 400 mg by mouth daily). Eligible participants were not previously exposed …


Safety And Efficacy Of Pembrolizumab In Combination With Acalabrutinib In Advanced Head And Neck Squamous Cell Carcinoma: Phase 2 Proof-Of-Concept Study, Matthew H Taylor, Courtney B Betts, Lauren Maloney, Eric Nadler, Alain Algazi, Michael J Guarino, John Nemunaitis, Antonio Jimeno, Priti Patel, Veerendra Munugalavadla, Lin Tao, Douglas Adkins, Jerome H Goldschmidt, Ezra E W Cohen, Lisa M Coussens Mar 2022

Safety And Efficacy Of Pembrolizumab In Combination With Acalabrutinib In Advanced Head And Neck Squamous Cell Carcinoma: Phase 2 Proof-Of-Concept Study, Matthew H Taylor, Courtney B Betts, Lauren Maloney, Eric Nadler, Alain Algazi, Michael J Guarino, John Nemunaitis, Antonio Jimeno, Priti Patel, Veerendra Munugalavadla, Lin Tao, Douglas Adkins, Jerome H Goldschmidt, Ezra E W Cohen, Lisa M Coussens

Open Access Publications

PURPOSE: Programmed cell death-1 (PD-1) receptor inhibitors have shown efficacy in head and neck squamous cell carcinoma (HNSCC), but treatment failure or secondary resistance occurs in most patients. In preclinical murine carcinoma models, inhibition of Bruton's tyrosine kinase (BTK) induces myeloid cell reprogramming that subsequently bolsters CD8+ T cell responses, resulting in enhanced antitumor activity. This phase 2, multicenter, open-label, randomized study evaluated pembrolizumab (anti-PD-1 monoclonal antibody) plus acalabrutinib (BTK inhibitor) in recurrent or metastatic HNSCC.

PATIENTS AND METHODS: Patients received pembrolizumab 200 mg intravenously every 3 weeks, alone or in combination with acalabrutinib 100 mg orally twice daily. Safety …


Transcriptomic Profile Investigations Highlight A Putative Role For Nudt16 In Sepsis, Susie Shih Yin Huang, Darawan Rinchai, Mohammed Toufiq, Basirudeen Syed Ahamed Kabeer, Jessica Roelands, Wouter Hendrickx, Sabri Boughorbel, Davide Bedognetti, Nicholas Van Panhuys, Damien Chaussabel, Mathieu Garand Mar 2022

Transcriptomic Profile Investigations Highlight A Putative Role For Nudt16 In Sepsis, Susie Shih Yin Huang, Darawan Rinchai, Mohammed Toufiq, Basirudeen Syed Ahamed Kabeer, Jessica Roelands, Wouter Hendrickx, Sabri Boughorbel, Davide Bedognetti, Nicholas Van Panhuys, Damien Chaussabel, Mathieu Garand

Open Access Publications

Sepsis is an aberrant systemic inflammatory response mediated by the acute activation of the innate immune system. Neutrophils are important contributors to the innate immune response that controls the infection, but harbour the risk of collateral tissue damage such as thrombosis and organ dysfunction. A better understanding of the modulations of cellular processes in neutrophils and other blood cells during sepsis is needed and can be initiated via transcriptomic profile investigations. To that point, the growing repertoire of publicly accessible transcriptomic datasets serves as a valuable resource for discovering and/or assessing the robustness of biomarkers. We employed systematic literature mining, …


Social Isolation And Incident Heart Failure Hospitalization In Older Women: Women's Health Initiative Study Findings, Crystal W Cené, Xiaoyan Iris Leng, Khushnood Faraz, Matthew Allison, Khadijah Breathett, Chloe Bird, Mace Coday, Giselle Corbie-Smith, Randi Foraker, Nkechinyere N Ijioma, Milagros C Rosal, Shawnita Sealy-Jefferson, Tetyana P Shippee, Candyce H Kroenke Mar 2022

Social Isolation And Incident Heart Failure Hospitalization In Older Women: Women's Health Initiative Study Findings, Crystal W Cené, Xiaoyan Iris Leng, Khushnood Faraz, Matthew Allison, Khadijah Breathett, Chloe Bird, Mace Coday, Giselle Corbie-Smith, Randi Foraker, Nkechinyere N Ijioma, Milagros C Rosal, Shawnita Sealy-Jefferson, Tetyana P Shippee, Candyce H Kroenke

Open Access Publications

Background The association of social isolation or lack of social network ties in older adults is unknown. This knowledge gap is important since the risk of heart failure (HF) and social isolation increase with age. The study examines whether social isolation is associated with incident HF in older women, and examines depressive symptoms as a potential mediator and age and race and ethnicity as effect modifiers. Methods and Results This study included 44 174 postmenopausal women of diverse race and ethnicity from the WHI (Women's Health Initiative) study who underwent annual assessment for HF adjudication from baseline enrollment (1993-1998) through …