Hypersensitivity reactions to human papillomavirus vaccine in Australian schoolgirls: retrospective cohort study

Objective To describe the outcomes of clinical evaluation, skin testing, and vaccine challenge in adolescent schoolgirls with suspected hypersensitivity to the quadrivalent human papillomavirus vaccine introduced in Australian schools in 2007

Clearance of Genotype 1b Hepatitis C Virus in Chimpanzees in the Presence of Vaccine-Induced E1-Neutralizing Antibodies

Accumulating evidence indicates that neutralizing antibodies play an important role in protection from chronic hepatitis C virus (HCV) infection. Efforts to elicit such responses by immunization with intact heterodimeric E1E2 envelope proteins have met with limited success. To determine whether antigenic sites, which are not exposed by the combined E1E2 heterodimer structure, are capable of eliciting neutralizing antibody responses, we expressed and purified each as separate recombinant proteins E1 and E2, from which the immunodominant hypervariable region (HVR-1) was deleted. Immunization of chimpanzees with either E1 or E2 alone induced antigen-specific T-helper cytokines of similar magnitude. Unexpectedly, the capacity to neutralize HCV was observed in E1 but not in animals immunized with E2 devoid of HVR-1. Furthermore, in vivo only E1-vaccinated animals exposed to the heterologous HCV-1b inoculum cleared HCV infection

Report of the 1st Workshop on Generative AI and Law

This report presents the takeaways of the inaugural Workshop on Generative AI and Law (GenLaw), held in July 2023. A cross-disciplinary group of practitioners and scholars from computer science and law convened to discuss the technical, doctrinal, and policy challenges presented by law for Generative AI, and by Generative AI for law, with an emphasis on U.S. law in particular. We begin the report with a high-level statement about why Generative AI is both immensely significant and immensely challenging for law. To meet these challenges, we conclude that there is an essential need for 1) a shared knowledge base that provides a common conceptual language for experts across disciplines; 2) clarification of the distinctive technical capabilities of generative-AI systems, as compared and contrasted to other computer and AI systems; 3) a logical taxonomy of the legal issues these systems raise; and, 4) a concrete research agenda to promote collaboration and knowledge-sharing on emerging issues at the intersection of Generative AI and law. In this report, we synthesize the key takeaways from the GenLaw workshop that begin to address these needs. All of the listed authors contributed to the workshop upon which this report is based, but they and their organizations do not necessarily endorse all of the specific claims in this report

An exercise-based international polymer syllabus

The IUPAC Subcommittee on Polymer Education has been pursuing the development of a compact syllabus covering the essential topics required for a tertiary education in polymer science, with numerical and short answer exercises addressing each topic. The primary goal of the document is to provide a framework for a complete course made freely available worldwide so that any educator can implement a professionally-curated course in polymer science for their students without needing expensive textbooks or reliable internet access. An important secondary goal is to popularize the use of approved IUPAC terminology in polymer science by using it consistently throughout the document and providing references to IUPAC source documents. Professor Melissa Chin Han Chan was an active and enthusiastic participant in the project who played a significant role in its design and implementation. The late Professor Richard ‘Dick’ Jones also had a keen interest in the project and had a great influence on its direction and structure. This brief note is dedicated to these two illustrious polymer scientists

Inflammatory phenotypes in patients with severe asthma are associated with distinct airway microbiology

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Background Asthma pathophysiology and treatment responsiveness are predicted by inflammatory phenotype. However, the relationship between airway microbiology and asthma phenotype is poorly understood. Objective We aimed to characterize the airway microbiota in patients with symptomatic stable asthma and relate composition to airway inflammatory phenotype and other phenotypic characteristics. Methods The microbial composition of induced sputum specimens collected from adult patients screened for a multicenter randomized controlled trial was determined by using 16S rRNA gene sequencing. Inflammatory phenotypes were defined by sputum neutrophil and eosinophil cell proportions. Microbiota were defined by using α- and β-diversity measures, and interphenotype differences were identified by using similarity of percentages, network analysis, and taxon fold change. Phenotypic predictors of airway microbiology were identified by using multivariate linear regression. Results Microbiota composition was determined in 167 participants and classified as eosinophilic (n = 84), neutrophilic (n = 14), paucigranulocytic (n = 60), or mixed neutrophilic-eosinophilic (n = 9) asthma phenotypes. Airway microbiology was significantly less diverse (P = .022) and more dissimilar (P = .005) in neutrophilic compared with eosinophilic participants. Sputum neutrophil proportions, but not eosinophil proportions, correlated significantly with these diversity measures (α-diversity: Spearman r = −0.374, P < .001; β-diversity: r = 0.238, P = .002). Interphenotype differences were characterized by a greater frequency of pathogenic taxa at high relative abundance and reduced Streptococcus, Gemella, and Porphyromonas taxa relative abundance in patients with neutrophilic asthma. Multivariate regression confirmed that sputum neutrophil proportion was the strongest predictor of microbiota composition. Conclusions Neutrophilic asthma is associated with airway microbiology that is significantly different from that seen in patients with other inflammatory phenotypes, particularly eosinophilic asthma. Differences in microbiota composition might influence the response to antimicrobial and steroid therapies and the risk of lung infection

Screening ethnically diverse human embryonic stem cells identifies a chromosome 20 minimal amplicon conferring growth advantage

The International Stem Cell Initiative analyzed 125 human embryonic stem (ES) cell lines and 11 induced pluripotent stem (iPS) cell lines, from 38 laboratories worldwide, for genetic changes occurring during culture. Most lines were analyzed at an early and late passage. Single-nucleotide polymorphism (SNP) analysis revealed that they included representatives of most major ethnic groups. Most lines remained karyotypically normal, but there was a progressive tendency to acquire changes on prolonged culture, commonly affecting chromosomes 1, 12, 17 and 20. DNA methylation patterns changed haphazardly with no link to time in culture. Structural variants, determined from the SNP arrays, also appeared sporadically. No common variants related to culture were observed on chromosomes 1, 12 and 17, but a minimal amplicon in chromosome 20q11.21, including three genes expressed in human ES cells, ID1, BCL2L1 and HM13, occurred in >20% of the lines. Of these genes, BCL2L1 is a strong candidate for driving culture adaptation of ES cells

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Correction to: Cluster identification, selection, and description in Cluster randomized crossover trials: the PREP-IT trials

An amendment to this paper has been published and can be accessed via the original article