A Fentanyl Hapten-Displaying Lipid Nanoparticle Vaccine that Non-Covalently Encapsulates a TLR7/8 Agonist and T-Helper Epitope Induces Protective Anti-Fentanyl Immunity.

Opioid use disorder - particularly involving fentanyl - has precipitated a public health crisis characterized by a significant increase in addiction and overdose-related deaths. Fentanyl-specific immunotherapy, which aims at inducing fentanyl-specific antibodies capable of binding fentanyl molecules in the bloodstream, preventing their entry in the central nervous system, is therefore gaining momentum. Conventional opioid designs rely on the covalent conjugation of fentanyl analogues to immunogenic carrier proteins that hold the inherent capacity of mounting immunodominant responses.

The effect of cycloplegia in the accuracy of autorefraction, keratometry and axial length using the Myopia Master.

Background: Assessing refractive errors under cycloplegia is recommended for paediatric patients; however, this may not always be feasible. In these situations, refraction has to rely on measurements made under active accommodation which may increase measurements variability and error. Therefore, evaluating the accuracy and precision of non-cycloplegic refraction and biometric measurements is clinically relevant.

Single-cell proteomics and transcriptomics capture eosinophil development and identify the role of IL-5 in their lineage transit amplification.

The activities, ontogeny, and mechanisms of lineage expansion of eosinophils are less well resolved than those of other immune cells, despite the use of biological therapies targeting the eosinophilia-promoting cytokine interleukin (IL)-5 or its receptor, IL-5Rα. We combined single-cell proteomics and transcriptomics and generated transgenic IL-5Rα reporter mice to revisit eosinophilopoiesis. We reconciled human and murine eosinophilopoiesis and provided extensive cell-surface immunophenotyping and transcriptomes at different stages along the continuum of eosinophil maturation.

How does active yeast supplementation reduce the deleterious effects of aflatoxins in Wistar rats? A radiolabeled assay and histopathological study.

The aim of this study was to investigate the mechanisms by which yeasts (Saccharomyces cerevisiae) control the toxic effects of aflatoxins, which are not yet fully understood. Radiolabeled aflatoxin B (AFBH) was administered by gavage to Wistar rats fed with aflatoxin (AflDiet) and aflatoxin supplemented with active dehydrated yeast Y904 (AflDiet + Yeast). The distribution of AFBH and its metabolites were analyzed at 24, 48 and 72 h by tracking back of the radioactivity.

Influence of anterior chamber depth and vault on anterior chamber angle morphology after phakic posterior chamber intraocular lens implantation.

Purpose: This study aims to investigate the influence of anterior chamber depth (ACD) and vault on the anterior chamber angle (ACA) morphology in myopic individuals implanted with posterior chamber phakic intraocular lenses.

Methods: This retrospective case series involved 231 eyes receiving a 13.2-mm implantable collamer lens (ICL).

Surgical treatment of an all-spine epidural empyema.

Spinal epidural empyema (SEE) is a severe infectious disease of the spine which may cause significant morbidity and mortality. Surgical drainage of the empyema is a key feature. However, approach-related morbidity may be significant in very extensive collections.

A multi-task convolutional neural network for classification and segmentation of chronic venous disorders.

Chronic Venous Disorders (CVD) of the lower limbs are one of the most prevalent medical conditions, affecting 35% of adults in Europe and North America. Due to the exponential growth of the aging population and the worsening of CVD with age, it is expected that the healthcare costs and the resources needed for the treatment of CVD will increase in the coming years. The early diagnosis of CVD is fundamental in treatment planning, while the monitoring of its treatment is fundamental to assess a patient's condition and quantify the evolution of CVD.

Repeatability and agreement of swept-source optical coherence tomography and partial coherence interferometry biometers in myopes.

Clinical Relevance: Biometric measurements in the context of myopia are fundamental to detect eyes at risk of developing myopia and during the follow-up of patients with myopia control treatment. Thus, the accuracy of biometers has high clinical relevance.

Background: The Myopia Master is a new biometer based on partial coherence interferometry especially dedicated to the follow-up of myopic patients.

Vault differences in eyes implanted with spherical and toric implantable collamer lenses: an inter-eye analysis.

Purpose: To determine the influence of implantable collamer lenses (ICL) geometry, i.e. spherical and toric on the vault, and report the refractive and visual outcomes of patients bilaterally implanted with the two ICL geometries.

Computational Study of the pH-Dependent Ionic Environment around β-Lactoglobulin.

Ions are involved in multiple biological processes and may exist bound to biomolecules or may be associated with their surface. Although the presence of ions in nucleic acids has traditionally gained more interest, ion-protein interactions, often with a marked dependency on pH, are beginning to gather attention. Here we present a detailed analysis on the binding and distribution of ions around β-lactoglobulin using a constant-pH MD (CpHMD) method, at a pH range 3-8, and compare it with the more traditional Poisson-Boltzmann (PB) model and the existing experimental data.

Characterization of the Workspace and Limits of Operation of Laser Treatments for Vascular Lesions of the Lower Limbs.

The increase of the aging population brings numerous challenges to health and aesthetic segments. Here, the use of laser therapy for dermatology is expected to increase since it allows for non-invasive and infection-free treatments. However, existing laser devices require doctors' manually handling and visually inspecting the skin.

FixBox: A General Algorithm to Fix Molecular Systems in Periodic Boxes.

Periodic boundary conditions (PBCs) are a standard feature of molecular simulations, and their mathematical and computational aspects are well-understood and relatively straightforward. However, they can in practice be a nuisance when simulating heterogeneous systems, especially when different types of molecules change their relative positions during the simulation. Although the translation required to fix a broken molecular complex of interest can in most cases be easily inferred by visual inspection, it typically depends on the type of system, its configuration, and the box geometry, making automated procedures problematic.

Classification of Chronic Venous Disorders using an Ensemble Optimization of Convolutional Neural Networks.

Chronic Venous Disorders (CVD) of lower limbs are one of the most prevalent medical conditions, affecting 35% of adults in Europe and North America. The early diagnosis of CVD is critical, however, the diagnosis relies on a visual recognition of the various venous disorders which is time- consuming and dependent on the physician's expertise. Thus, automatic strategies for the classification of the CVD severity are claimed.

TGF-β regulates the stem-like state of PD-1+ TCF-1+ virus-specific CD8 T cells during chronic infection.

Recent studies have defined a novel population of PD-1+ TCF-1+ stem-like CD8 T cells in chronic infections and cancer. These quiescent cells reside in lymphoid tissues, are critical for maintaining the CD8 T cell response under conditions of persistent antigen, and provide the proliferative burst after PD-1 blockade. Here we examined the role of TGF-β in regulating the differentiation of virus-specific CD8 T cells during chronic LCMV infection of mice.

Approach to Study pH-Dependent Protein Association Using Constant-pH Molecular Dynamics: Application to the Dimerization of β-Lactoglobulin.

Protein-protein association is often mediated by electrostatic interactions and modulated by pH. However, experimental and computational studies have often overlooked the effect of association on the protonation state of the protein. In this work, we present a methodological approach based on constant-pH molecular dynamics (MD), which aims to provide a detailed description of a pH-dependent protein-protein association, and apply it to the dimerization of β-lactoglobulin (BLG).

Accommodative and binocular vision dysfunctions in a Portuguese clinical population.

Background: Several studies have suggested that accommodative and non-strabismic binocular dysfunctions are commonly encountered in optometric practice. This study aims to verify whether these findings apply to a Portuguese clinical population.

Methods: This study included consecutive nonpresbyopic subjects that came to two Portuguese optometric clinics over a period of six months.

Author Correction: Commensal-driven immune zonation of the liver promotes host defence.

A Correction to this paper has been published: https://doi.org/10.1038/s41586-021-03346-0.

Association between Clinical Vision Measures and Visual Perception and Soccer Referees' On-field Performance.

Significance: The decisions taken by soccer officials are critically important to game management. Understanding the underlying processes that mediate expert performance in soccer refereeing may lead to a better standard of officiating. Vision is the dominant source of incoming information upon which officials rely to make their on-field decisions.

Biometric and ICL-related risk factors associated to sub-optimal vaults in eyes implanted with implantable collamer lenses.

Background: To identify biometric and implantable collamer lens (ICL)-related risk factors associated with sub-optimal postoperative vault in eyes implanted with phakic ICL.

Methods: This study reports a retrospective case series of the first operated eye in 360 patients implanted with myopic spherical or toric ICL. Preoperatively, white-to-white (WTW), central keratometry (Kc) and central corneal thickness (CCT) were measured using the Pentacam.

ILC3s control splenic cDC homeostasis via lymphotoxin signaling.

The spleen contains a myriad of conventional dendritic cell (cDC) subsets that protect against systemic pathogen dissemination by bridging antigen detection to the induction of adaptive immunity. How cDC subsets differentiate in the splenic environment is poorly understood. Here, we report that LTα1β2-expressing Rorgt+ ILC3s, together with B cells, control the splenic cDC niche size and the terminal differentiation of Sirpα+CD4+Esam+ cDC2s, independently of the microbiota and of bone marrow pre-cDC output.