Recent work has demonstrated that temporary crosslinks in polymer networks generated by chemical "fuels" afford materials with large, transient changes in their mechanical properties. This can be accomplished in carboxylic-acid-functionalized polymer hydrogels using carbodiimides, which generate anhydride crosslinks with lifetimes on the order of minutes to hours. Here, the impact of the polymer network architecture on the mechanical properties of transiently crosslinked materials was explored.
View Article and Find Full Text PDFIntroduction: This prospective, longitudinal, community-based study, EpidemiologiCal POpulatioN STudy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Lake CounTy, Illinois (CONTACT), investigated coronavirus disease 2019 (COVID-19) immunity, occupational risks related to SARS-CoV-2 exposure, and long-term immunoglobulin G (IgG) seroconversion kinetics.
Methods: At baseline and follow up (3, 6, and 9 months), non-hospitalized adult participants provided nasal and blood serum specimens for molecular [reverse transcription polymerase chain reaction (RT-PCR)] and serological (IgG) testing (4 November 2020-30 October 2021).
Results: At baseline, 6.
Introduction: The COVID-19 pandemic has caused over 6 million deaths worldwide and is a significant cause of mortality. Mortality dynamics vary significantly by country due to pathogen, host, social and environmental factors, in addition to vaccination and treatments. However, there is limited data on the relative contribution of different explanatory variables, which may explain changes in mortality over time.
View Article and Find Full Text PDFBackground: Certain immune-mediated inflammatory diseases (IMIDs) may increase patients' risk for venous thromboembolisms (VTEs), yet how atopic dermatitis (AD) influences VTE risk remains unclear.
Objective: Describe VTE incidence in patients with AD compared with other IMIDs and unaffected, AD-matched controls.
Methods: This retrospective, observational, comparative cohort study used Optum Clinformatics United States claims data (2010-2019) of adults with AD, rheumatoid arthritis (RA), Crohn's disease (CD), ulcerative colitis (UC), psoriasis (PsO), psoriatic arthritis (PsA), or ankylosing spondylitis (AS).
Introduction: To evaluate factors associated with severe coronavirus disease 2019 (COVID-19) among patients with rheumatoid arthritis (RA) in the US.
Methods: Adults with RA who had a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, based on molecular or antigen test or clinical diagnosis, were identified from the Optum COVID-19 Electronic Health Record dataset (March 1, 2020-April 28, 2021). The primary outcome was the occurrence of severe COVID-19 (hospitalization or death) within 30 days from SARS-CoV-2 infection.
Background: Atopic dermatitis (AD) is severely burdensome, and there has been poor characterization of any differences in impact based on the area affected.
Objective: To estimate the prevalence and HRQoL impact of head/face/neck/hand (HFNH) involvement among patients with moderate-to-severe atopic dermatitis.
Methods: All TARGET-DERM AD registry patients with moderate/severe Investigator Global Assessment (vIGA-AD) were assessed using the Patient Oriented SCORing Atopic Dermatitis, Patient Oriented Eczema Measure (POEM) and the (Children's) Dermatology Life Quality Index ((C)DLQI).
Background: Research examining associations between the clinician-reported validated Investigator Global Assessment for AD (vIGA-AD) and patient-reported disease burden is sparse. This study aims to evaluate the relationship between vIGA-AD with patient-reported disease severity and quality of life (QoL).
Methods: A cross-sectional analysis was conducted using a September 2021 data cut from the TARGET-DERM AD study, a real-world, longitudinal cohort of children, adolescents, and adults with AD enrolled at 44 academic and community dermatology and allergy sites in the US.
Introduction: There are concerns that patients in an immunocompromised state may be at risk for increased coronavirus disease 2019 (COVID-19) severity. The aim of this study was to describe the characteristics of patients with COVID-19 and immune-mediated inflammatory diseases (IMIDs) or malignancies and evaluate their risk of developing severe COVID-19.
Methods: Cases of COVID-19 (ICD-10 code U07.
Purpose: This case-control study investigated the long-term evolution of multidrug-resistant bacteria (MDRB) over a 5-year period associated with the use of selective oropharyngeal decontamination (SOD) in the intensive care unit (ICU). In addition, effects on health care-associated infections and ICU mortality were analysed.
Methods: We investigated patients undergoing mechanical ventilation > 48 h in 11 adult ICUs located at 3 campuses of a university hospital.
Background: Previous observational studies utilizing administrative claims data have largely been unable to consider clinical factors that may be related to patterns of drug use among patients with rheumatoid arthritis (RA).
Objective: To understand predictors of treatment changes following initiation of a tumor necrosis factor inhibitor (TNFi) using nation-wide electronic health record (EHR) data in the USA.
Methods: The Optum Immunology Condition EHR data (01/01/2011-09/30/2019) was used to identify a population of adult patients with RA initiating a TNFi as the first line biologic disease-modifying anti-rheumatic drug (DMARD).
Introduction: EpidemiologiCal POpulatioN STudy of SARS-CoV-2 in Lake CounTy, Illinois (CONTACT) is an observational, epidemiological study with a 9-month longitudinal follow-up of nonhospitalized persons aged 18 years or older currently living or employed in Lake County, IL. We describe the study design and report baseline characteristics of the study participants, including the proportion of participants with acute or previous SARS-CoV-2 infection at enrollment.
Methods: At enrollment and subsequent timepoints, participants recruited through digital and paper-based advertising campaigns reported their occupational and school-based exposure, risk factors, and behaviors, and provided nasal and serum specimens.
Chimeric antigen receptor (CAR) T cell therapy has emerged as an attractive strategy for cancer immunotherapy. Despite remarkable success for hematological malignancies, excessive activity and poor control of CAR T cells can result in severe adverse events requiring control strategies to improve safety. This work illustrates the feasibility of a zinc finger-based inducible switch system for transcriptional regulation of an anti-CD20 CAR in primary T cells providing small molecule-inducible control over therapeutic functions.
View Article and Find Full Text PDFA substantial number of patients with leukemia and lymphoma treated with anti-CD19 or anti-CD22 monoCAR-T cell therapy relapse because of antigen loss or down-regulation. We hypothesized that B cell tumor antigen escape may be overcome by a chimeric antigen receptor (CAR) design that simultaneously targets three B cell leukemia antigens. We engineered trispecific duoCAR-T cells with lentiviral vectors encoding two CAR open reading frames that target CD19, CD20, and CD22.
View Article and Find Full Text PDFLentiviral vectors (LV) have emerged as a robust technology for therapeutic gene delivery into human cells as advanced medicinal products. As these products are increasingly commercialized, there are concomitant demands for their characterization to ensure safety, efficacy and consistency. Standards are essential for accurately measuring parameters for such product characterization.
View Article and Find Full Text PDFChimeric antigen receptor (CAR) T cells targeting CD19 are a breakthrough treatment for relapsed, refractory B cell malignancies. Despite impressive outcomes, relapse with CD19 disease remains a challenge. We address this limitation through a first-in-human trial of bispecific anti-CD20, anti-CD19 (LV20.
View Article and Find Full Text PDFChimeric antigen receptor T cells (CAR-T cell) targeting CD19 are effective against several subtypes of CD19-expressing hematologic malignancies. Centralized manufacturing has allowed rapid expansion of this cellular therapy, but it may be associated with treatment delays due to the required logistics. We hypothesized that point of care manufacturing of CAR-T cells on the automated CliniMACS Prodigy device allows reproducible and fast delivery of cells for the treatment of patients with non-Hodgkin lymphoma.
View Article and Find Full Text PDFIntroduction: The purpose of this study was to explore communication with health care providers from the perceptions of parents before their child's diagnosis of autism spectrum disorder and provide some examples of how communication may contribute to the autism diagnosis.
Method: This study used a qualitative descriptive design with multiple individual structured in-person interviews.
Results: Three themes captured parents' (n = 8) descriptions of the phases of communication during their children's diagnoses including, (1) anguished questioning, (2) urgently seeking help, and (3) expecting a diagnosis.
Dendritic cell (DC) aggresome-like induced structures (DALIS) are protein aggregates of polyubiquitylated proteins that form transiently during DC maturation. DALIS scatter randomly throughout the cytosol and serve as antigen storage sites synchronising DC maturation and antigen presentation. Maturation of DCs is accompanied by the induction of the ubiquitin-like modifier FAT10 (also known as UBD), which localises to aggresomes, structures that are similar to DALIS.
View Article and Find Full Text PDFThis review evaluates the role of mechanotransduction (MT) in heart failure (HF) pathobiology. Cardiac functional and structural modifications are regulated by biomechanical forces. Exposing cardiomyocytes and the myocardial tissue to altered biomechanical stress precipitates changes in the end-diastolic wall stress (EDWS).
View Article and Find Full Text PDFGenetic engineering is an important tool for redirecting the function of various types of immune cells and their use for therapeutic purpose. Although NK cells have many beneficial therapeutic features, genetic engineering of immune cells for targeted therapy focuses mostly on T cells. One of the major obstacles for NK cell immunotherapy is the lack of an efficient method for gene transfer.
View Article and Find Full Text PDFAdoptive immunotherapy using chimeric antigen receptor-modified T cells (CAR-T) has made substantial contributions to the treatment of certain B cell malignancies. Such treatment modalities could potentially obviate the need for long-term antiretroviral drug therapy in HIV/AIDS. Here, we report the development of HIV-1-based lentiviral vectors that encode CARs targeting multiple highly conserved sites on the HIV-1 envelope glycoprotein using a two-molecule CAR architecture, termed duoCAR.
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