Development and Validation of a Spontaneous Smile Assay

IMPORTANCE Smiling can be a voluntary or involuntarymovement. Facial reanimation procedures differ in their ability to restore a spontaneous smile, and an assay designed to evoke and evaluate a spontaneous smile is not available. OBJECTIVE To develop and validate an assay to assess the spontaneous smile of patients with facial paralysis. DESIGN, SETTING, AND PARTICIPANTS Thiswas an exploratory cohort study. A series of short video clips were administered to laypersons via an online survey service from January 1, 2014, to March 31, 2014. Respondents rated how funny each video was on a visual analog scale from 0 to 100. The 4 funniest videos were selected to generate a 11/2-minute spontaneous smile assay. The assay was then administered from July 1, 2014, to December 31, 2014, to 2 different study groups: the first was composed of 100 healthy individuals (control group) and the second was composed of 30 patients with facial paralysis.We analyzed the capability of this assay to provoke at least 1 spontaneous smile and calculated smile excursion in both groups. Statistical analysis was performed using analysis of variance. INTERVENTION Spontaneous smile assay administered to both healthy and diseased groups. MAIN OUTCOMES AND MEASURES Ability of the assay to elicit smiles, as defined by an oral commissure excursion greater than 3 mm, as well as difference in commissure excursion. RESULTS Ninety-five (95.0%) participants in the control group and 29 (96.7%) patients with facial paralysis experienced at least 1 oral commissure excursion that appeared to be a spontaneous smile while viewing the assay. Mean oral commissure excursion with spontaneous smile was 9.08mm(95%CI, 2.77-15.39) in controls, 6.72mm(95%CI, 3.13-10.31) on the healthy side in patients with flaccid facial paralysis (P=.004 vs controls), and 9.64mm(95%CI, 3.52-15.76) on the healthy side in patients with nonflaccid facial paralysis (P=.74). Among patients with flaccid facial paralysis, a statistically significant difference was found between smile excursion of the affected and the unaffected sides (P = .03). There was no statistically significant difference in the measurement between sides for the control group (P = .67). CONCLUSIONS AND RELEVANCE Although humor is a challenging construct to universalize, our assay was able to elicit a smile in almost all individuals in the group with facial paralysis and the control group. The spontaneous smile assay will facilitate future research on the ability of facial reanimation procedures and other interventions to restore a spontaneous smile

Clinical Data: Sources and Types, Regulatory Constraints, Applications.

Access to clinical data is critical for the advancement of translational research. However, the numerous regulations and policies that surround the use of clinical data, although critical to ensure patient privacy and protect against misuse, often present challenges to data access and sharing. In this article, we provide an overview of clinical data types and associated regulatory constraints and inferential limitations. We highlight several novel approaches that our team has developed for openly exposing clinical data

Broadly neutralizing human monoclonal antibodies to the hepatitis C virus E2 glycoprotein

The humoral response to hepatitis C virus (HCV) may contribute to controlling infection. We previously isolated human monoclonal antibodies to conformational epitopes on the HCV E2 glycoprotein. Here, we report on their ability to inhibit infection by retroviral pseudoparticles incorporating a panel of full-length E1E2 clones representing the full spectrum of genotypes 1–6. We identified one antibody, CBH-5, that was capable of neutralizing every genotype tested. It also potently inhibited chimeric cell culture-infectious HCV, which had genotype 2b envelope proteins in a genotype 2a (JFH-1) background. Analysis using a panel of alanine-substitution mutants of HCV E2 revealed that the epitope of CBH-5 includes amino acid residues that are required for binding of E2 to CD81, a cellular receptor essential for virus entry. This suggests that CBH-5 inhibits HCV infection by competing directly with CD81 for a binding site on E2

Hepatitis C Virus E2 Has Three Immunogenic Domains Containing Conformational Epitopes with Distinct Properties and Biological Functions

Mechanisms of virion attachment, interaction with its receptor, and cell entry are poorly understood for hepatitis C virus (HCV) because of a lack of an efficient and reliable in vitro system for virus propagation. Infectious HCV retroviral pseudotype particles (HCVpp) were recently shown to express native E1E2 glycoproteins, as defined in part by HCV human monoclonal antibodies (HMAbs) to conformational epitopes on E2, and some of these antibodies block HCVpp infection (A. Op De Beeck, C. Voisset, B. Bartosch, Y. Ciczora, L. Cocquerel, Z. Y. Keck, S. Foung, F. L. Cosset, and J. Dubuisson, J. Virol. 78:2994-3002, 2004). Why some HMAbs are neutralizing and others are nonneutralizing is looked at in this report by a series of studies to determine the expression of their epitopes on E2 associated with HCVpp and the role of antibody binding affinity. Antibody cross-competition defined three E2 immunogenic domains with neutralizing HMAbs restricted to two domains that were also able to block E2 interaction with CD81, a putative receptor for HCV. HCVpp immunoprecipitation showed that neutralizing and nonneutralizing domains are expressed on E2 associated with HCVpp, and affinity studies found moderate-to-high-affinity antibodies in all domains. These findings support the perspective that HCV-specific epitopes are responsible for functional steps in virus infection, with specific antibodies blocking distinct steps of virus attachment and entry, rather than the perspective that virus neutralization correlates with increased antibody binding to any virion surface site, independent of the epitope recognized by the antibody. Segregation of virus neutralization and sensitivity to low pH to specific regions supports a model of HCV E2 immunogenic domains similar to the antigenic structural and functional domains of other flavivirus envelope E glycoproteins

Corticosteroid use in otolaryngology: current considerations during the COVID-19 era

Objective To offer pragmatic, evidence-informed advice on administering corticosteroids in otolaryngology during the coronavirus disease 2019 (COVID-19) pandemic, considering therapeutic efficacy, potential adverse effects, susceptibility to COVID-19, and potential effects on efficacy of vaccination against SARS-CoV-2, which causes COVID-19. Data Sources PubMed, Cochrane Library, EMBASE, CINAHL, and guideline databases. Review Methods Guideline search strategies, supplemented by database searches on sudden sensorineural hearing loss (SSNHL), idiopathic facial nerve paralysis (Bell’s palsy), sinonasal polyposis, laryngotracheal disorders, head and neck oncology, and pediatric otolaryngology, prioritizing systematic reviews, randomized controlled trials, and COVID-19–specific findings. Conclusions Systemic corticosteroids (SCSs) reduce long-term morbidity in individuals with SSNHL and Bell’s palsy, reduce acute laryngotracheal edema, and have benefit in perioperative management for some procedures. Topical or locally injected corticosteroids are preferable for most other otolaryngologic indications. SCSs have not shown long-term benefit for sinonasal disorders. SCSs are not a contraindication to vaccination with COVID-19 vaccines approved by the US Food and Drug Administration. The Centers for Disease Control and Prevention noted that these vaccines are safe for immunocompromised patients. Implications for Practice SCS use for SSNHL, Bell’s palsy, laryngotracheal edema, and perioperative care should follow prepandemic standards. Local or topical corticosteroids are preferable for most other otolaryngologic indications. Whether SCSs attenuate response to vaccination against COVID-19 or increase susceptibility to SARS-CoV-2 infection is unknown. Immunosuppression may lower vaccine efficacy, so immunocompromised patients should adhere to recommended infection control practices. COVID-19 vaccination with Pfizer-BioNTech, Moderna, or Johnson & Johnson vaccines is safe for immunocompromised patients

Sex, obesity, diabetes, and exposure to particulate matter among patients with severe asthma: Scientific insights from a comparative analysis of open clinical data sources during a five-day hackathon.

This special communication describes activities, products, and lessons learned from a recent hackathon that was funded by the National Center for Advancing Translational Sciences via the Biomedical Data Translator program (\u27Translator\u27). Specifically, Translator team members self-organized and worked together to conceptualize and execute, over a five-day period, a multi-institutional clinical research study that aimed to examine, using open clinical data sources, relationships between sex, obesity, diabetes, and exposure to airborne fine particulate matter among patients with severe asthma. The goal was to develop a proof of concept that this new model of collaboration and data sharing could effectively produce meaningful scientific results and generate new scientific hypotheses. Three Translator Clinical Knowledge Sources, each of which provides open access (via Application Programming Interfaces) to data derived from the electronic health record systems of major academic institutions, served as the source of study data. Jupyter Python notebooks, shared in GitHub repositories, were used to call the knowledge sources and analyze and integrate the results. The results replicated established or suspected relationships between sex, obesity, diabetes, exposure to airborne fine particulate matter, and severe asthma. In addition, the results demonstrated specific differences across the three Translator Clinical Knowledge Sources, suggesting cohort- and/or environment-specific factors related to the services themselves or the catchment area from which each service derives patient data. Collectively, this special communication demonstrates the power and utility of intense, team-oriented hackathons and offers general technical, organizational, and scientific lessons learned