Polymers, lipids, scaffolds, microneedles, and other biomaterials are rapidly emerging as technologies to improve the efficacy of vaccines against infectious disease and immunotherapies for cancer, ...autoimmunity, and transplantation. New studies are also providing insight into the interactions between these materials and the immune system. This insight can be exploited for more efficient design of vaccines and immunotherapies. Here, we describe recent advances made possible through the unique features of biomaterials, as well as the important questions for further study.
Biomaterials have intrinsic immunogenic features (size, shape, and chemistry) that can be harnessed to create carriers that actively direct responses to vaccines and immunotherapies, or to modify immune cell function in vivo.
Biomaterials can provide control over the combinations and relative concentrations of ligands to simultaneously target multiple immune populations and pathways, or to target these signals to specific cells, organelles, or tissues.
In addition to immunogenic properties, biomaterials can support decreased systemic effects and pain, improved cargo stability, and enable self-administration in developing geographic regions.
Increased collaboration between material scientists and immunologists may enable the fast integration of emerging understanding in both fields.
Amazon’s Mechanical Turk (MTurk) is an increasingly popular tool for the recruitment of research subjects. While there has been much focus on the demographic differences between MTurk samples and the ...national public, we know little about whether liberals and conservatives recruited from MTurk share the same psychological dispositions as their counterparts in the mass public. In the absence of such evidence, some have argued that the selection process involved in joining MTurk invalidates the subject pool for studying questions central to political science. In this paper, we evaluate this claim by comparing a large MTurk sample to two benchmark national samples – one conducted online and one conducted face-to-face. We examine the personality and value-based motivations of political ideology across the three samples. All three samples produce substantively identical results with only minor variation in effect sizes. In short, liberals and conservatives in our MTurk sample closely mirror the psychological divisions of liberals and conservatives in the mass public, though MTurk liberals hold more characteristically liberal values and attitudes than liberals from representative samples. Overall, our results suggest that MTurk is a valid recruitment tool for psychological research on political ideology.
Health equity and antiracism can contribute to enhanced patient safety in healthcare settings. The Oath of the Pharmacist states, “I will promote inclusion, embrace diversity, and advocate for ...justice to advance health equity.” Part of this commitment means upholding these principles in patient care settings. Racial and ethnic harm negatively impact patient safety. Racial and ethnic harm are reviewed in the context of social learning theory, critical race theory, and medical and scientific racism. Pharmacists and healthcare systems must actively prevent and mitigate racial and ethnic harm to patients from personal and organizational levels to create a culture of safety. Part of this strategy involves acknowledging when you have contributed to patient harm, issuing a genuine apology, and offering to mend or re-establish trust between racially and ethnically minoritized patients and the pharmacist or the health system to contribute to patient safety. These strategies may help create a culturally safe space for racially and ethnically marginalized patients in the healthcare system.
•Pharmacists should actively minimize and mitigate racial and ethnic harm to patients in the health care system.•Patinet racial-ethnic harm is reviewed via social learning theory, critical race theory, and scientific / medical racism.•Proactive strategies can help mend and strengthen relationships between the healthcare system and marginalized patients.•Pharmacists and the healthcare system must collaborate to create a culture of safety for marginalized patients.
Lack of coordination between screening studies for common mental disorders in primary care and community epidemiological samples impedes progress in clinical epidemiology. Short screening scales ...based on the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI), the diagnostic interview used in community epidemiological surveys throughout the world, were developed to address this problem.
Expert reviews and cognitive interviews generated CIDI screening scale (CIDI-SC) item pools for 30-day DSM-IV-TR major depressive episode (MDE), generalized anxiety disorder (GAD), panic disorder (PD) and bipolar disorder (BPD). These items were administered to 3058 unselected patients in 29 US primary care offices. Blinded SCID clinical reinterviews were administered to 206 of these patients, oversampling screened positives.
Stepwise regression selected optimal screening items to predict clinical diagnoses. Excellent concordance area under the receiver operating characteristic curve (AUC) was found between continuous CIDI-SC and DSM-IV/SCID diagnoses of 30-day MDE (0.93), GAD (0.88), PD (0.90) and BPD (0.97), with only 9-38 questions needed to administer all scales. CIDI-SC versus SCID prevalence differences are insignificant at the optimal CIDI-SC diagnostic thresholds (χ2 1 = 0.0-2.9, p = 0.09-0.94). Individual-level diagnostic concordance at these thresholds is substantial (AUC 0.81-0.86, sensitivity 68.0-80.2%, specificity 90.1-98.8%). Likelihood ratio positive (LR+) exceeds 10 and LR- is 0.1 or less at informative thresholds for all diagnoses.
CIDI-SC operating characteristics are equivalent (MDE, GAD) or superior (PD, BPD) to those of the best alternative screening scales. CIDI-SC results can be compared directly to general population CIDI survey results or used to target and streamline second-stage CIDIs.
Many experimental therapies for autoimmune diseases, such as multiple sclerosis (MS), aim to bias T cells toward tolerogenic phenotypes without broad suppression. However, the link between local ...signal integration in lymph nodes (LNs) and the specificity of systemic tolerance is not well understood. We used intra-LN injection of polymer particles to study tolerance as a function of signals in the LN microenvironment. In a mouse MS model, intra-LN introduction of encapsulated myelin self-antigen and a regulatory signal (rapamycin) permanently reversed paralysis after one treatment during peak disease. Therapeutic effects were myelin specific, required antigen encapsulation, and were less potent without rapamycin. This efficacy was accompanied by local LN reorganization, reduced inflammation, systemic expansion of regulatory T cells, and reduced T cell infiltration to the CNS. Our findings suggest that local control over signaling in distinct LNs can promote cell types and functions that drive tolerance that is systemic but antigen specific.
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•A single intra-lymph node (i.LN.) particle dose reverses autoimmunity/paralysis in mice•Efficacy is dependent on delivery of encapsulated self-antigen to lymph nodes (LNs)•i.LN. delivery of particles reprograms local LN cell composition and function•Altered local function in LNs promotes systemic but antigen-specific tolerance
Tostanoski et al. show that a single direct injection of degradable particles into lymph nodes reverses paralysis in a mouse model of multiple sclerosis underpinned by myelin attack. This local reprogramming of the lymph node microenvironment toward regulatory function drives tolerance that is systemic but myelin specific.
ABSTRACT
We present a first-look analysis of the JWST ERO data in the SMACS J0723.3-7327 cluster field. We begin by reporting 10 new spectroscopic redshifts from λobs = 1.8–5.2 μm NIRSpec ...medium-resolution (R = λ/Δλ = 1000) data. These are determined via multiple high-SNR emission line detections with five objects at 1 < z < 3 displaying multiple rest-frame near-infrared Hydrogen Paschen lines, and five objects at 5 < z < 9 displaying rest-frame optical Oxygen and Hydrogen Balmer lines. For the five higher-redshift galaxies we extract fluxes in six NIRCam bands spanning λobs = 0.8–5 μm and perform spectral energy distribution fitting in combination with existing HST photometry. The 7 < z < 9 objects exhibit a U-shaped pattern across the F277W, F356W, and F444W bands, indicating a Balmer break seen in emission (Balmer jump) and high-equivalent-width O iii emission. This indicates an extremely young stellar population with the bulk of the current mass having formed within the past 10 Myr. We report robust stellar masses and mean stellar ages from our spectral fitting with the four z > 6 galaxies exhibiting low-stellar masses from log10 (M*/M⊙) = 7.1–8.2, and correspondingly young mean stellar ages of only a few Myr. This work highlights the critical importance of combining large upcoming NIRCam surveys with NIRSpec follow-up to measure the spectroscopic redshifts necessary to robustly constrain physical parameters.
Bacteriophages, or phages, are viruses that specifically infect bacteria and coopt the cellular machinery to create more phage proteins, eventually resulting in the release of new phage particles. ...Phages are heavily utilized in bioengineering for applications ranging from tissue engineering scaffolds to immune signal delivery. Of specific interest to vaccines and immunotherapies, phages have demonstrated an ability to activate both the innate and adaptive immune systems. The genome of these viral particles can be harnessed for DNA vaccination, or the surface proteins can be exploited for antigen display. More specifically, genes that encode an antigen of interest can be spliced into the phage genome, allowing antigenic proteins or peptides to be displayed by fusion to phage capsid proteins. Phages therefore present antigens to immune cells in a highly ordered and repetitive manner. This review discusses the use of phage with adjuvanting activity as antigen delivery vehicles for vaccination against infectious disease and cancer.
ABSTRACT
Next‐generation sequencing has aided characterization of genomic variation. While whole‐genome sequencing may capture all possible mutations, whole‐exome sequencing remains cost‐effective ...and captures most phenotype‐altering mutations. Initial strategies for exome enrichment utilized a hybridization‐based capture approach. Recently, amplicon‐based methods were designed to simplify preparation and utilize smaller DNA inputs. We evaluated two hybridization capture‐based and two amplicon‐based whole‐exome sequencing approaches, utilizing both Illumina and Ion Torrent sequencers, comparing on‐target alignment, uniformity, and variant calling. While the amplicon methods had higher on‐target rates, the hybridization capture‐based approaches demonstrated better uniformity. All methods identified many of the same single‐nucleotide variants, but each amplicon‐based method missed variants detected by the other three methods and reported additional variants discordant with all three other technologies. Many of these potential false positives or negatives appear to result from limited coverage, low variant frequency, vicinity to read starts/ends, or the need for platform‐specific variant calling algorithms. All methods demonstrated effective copy‐number variant calling when evaluated against a single‐nucleotide polymorphism array. This study illustrates some differences between whole‐exome sequencing approaches, highlights the need for selecting appropriate variant calling based on capture method, and will aid laboratories in selecting their preferred approach.
Next generation sequencing has aided characterization of genomic variation. While whole genome sequencing remains costly, several whole exome sequencing technologies are available to detect phenotype‐altering mutations. We evaluated four such technologies to appraise sequencing uniformity and variant detection.
Multiple sclerosis (MS) is an autoimmune disease that develops when dysfunctional autoreactive lymphocytes attack the myelin sheath in the central nervous system. There are no cures for MS, and ...existing treatments are associated with unwanted side effects. One approach for treating MS is presenting distinct immune signals (i.e., self-antigen and immunomodulatory cues) to innate and adaptive immune cells to engage multiple signaling pathways involved in MS. We previously developed immune polyelectrolyte multilayer (iPEM) complexes built through layer-by-layer deposition of self-antigen - myelin oligodendrocyte glycoprotein (MOG) - and toll-like receptor antagonist, GpG to treat MS. Here, glutaraldehyde-mediated stable cross-links were integrated into iPEMs to load multiple classes of therapeutics. These cross-linked iPEMs maintain their immunological features, including the ability of GpG to blunt toll-like-receptor 9 signaling and MOG to expand T cells expressing myelin-specific T cell receptors. Lastly, we show that these functional assemblies can be loaded with a critical class of drug - mTOR inhibitors - associated with inducing regulatory T cells. These studies demonstrate the ability to incorporate small molecule drugs in reinforced self-assembled immune signals juxtaposed at high densities. This precision technology contributes new technologies that could drive antigen-specific immune response by simultaneously modulating innate and adaptive immunity.
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