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Hepatitis delta virus (HDV) and hepatitis B virus (HBV) are blood-borne viruses that infect human hepatocytes and cause significant liver disease. Infections with HBV are more damaging when there is a coinfection with HDV. The genomes and modes of replication of these two viruses are fundamentally different, except for the fact that, in nature, HDV replication is dependent upon the envelope proteins of HBV to achieve assembly and release of infectious virus particles, ones that use the same host cell receptor. This review focuses on what has been found of the various ways, natural and experimental, by which HDV particles can be assembled and released. This knowledge has implications for the prevention and treatment of HDV infections, and maybe for an understanding of the origin of HDV.

Purpose The translation of genome sequencing into routine health care has been slow, partly because of concerns about affordability. The aspirational cost of sequencing a genome is $1000, but there is little evidence to support this estimate. We estimate the cost of using genome sequencing in routine clinical care in patients with cancer or rare diseases. Methods We performed a microcosting study of Illumina-based genome sequencing in a UK National Health Service laboratory processing 399 samples/year. Cost data were collected for all steps in the sequencing pathway, including bioinformatics analysis and reporting of results. Sensitivity analysis identified key cost drivers. Results Genome sequencing costs £6841 per cancer case (comprising matched tumor and germline samples) and £7050 per rare disease case (three samples). The consumables used during sequencing are the most expensive component of testing (68–72% of the total cost). Equipment costs are higher for rare disease cases, whereas consumable and staff costs are slightly higher for cancer cases. Conclusion The cost of genome sequencing is underestimated if only sequencing costs are considered, and likely surpasses $1000/genome in a single laboratory. This aspirational sequencing cost will likely only be achieved if consumable costs are considerably reduced and sequencing is performed at scale.

Background Whole genome sequencing is increasingly being used for the diagnosis of patients with rare diseases. However, the diagnostic yields of many studies, particularly those conducted in a healthcare setting, are often disappointingly low, at 25–30%. This is in part because although entire genomes are sequenced, analysis is often confined to in silico gene panels or coding regions of the genome. Methods We undertook WGS on a cohort of 122 unrelated rare disease patients and their relatives (300 genomes) who had been pre-screened by gene panels or arrays. Patients were recruited from a broad spectrum of clinical specialties. We applied a bioinformatics pipeline that would allow comprehensive analysis of all variant types. We combined established bioinformatics tools for phenotypic and genomic analysis with our novel algorithms (SVRare, ALTSPLICE and GREEN-DB) to detect and annotate structural, splice site and non-coding variants. Results Our diagnostic yield was 43/122 cases (35%), although 47/122 cases (39%) were considered solved when considering novel candidate genes with supporting functional data into account. Structural, splice site and deep intronic variants contributed to 20/47 (43%) of our solved cases. Five genes that are novel, or were novel at the time of discovery, were identified, whilst a further three genes are putative novel disease genes with evidence of causality. We identified variants of uncertain significance in a further fourteen candidate genes. The phenotypic spectrum associated with RMND1 was expanded to include polymicrogyria. Two patients with secondary findings in FBN1 and KCNQ1 were confirmed to have previously unidentified Marfan and long QT syndromes, respectively, and were referred for further clinical interventions. Clinical diagnoses were changed in six patients and treatment adjustments made for eight individuals, which for five patients was considered life-saving. Conclusions Genome sequencing is increasingly being considered as a first-line genetic test in routine clinical settings and can make a substantial contribution to rapidly identifying a causal aetiology for many patients, shortening their diagnostic odyssey. We have demonstrated that structural, splice site and intronic variants make a significant contribution to diagnostic yield and that comprehensive analysis of the entire genome is essential to maximise the value of clinical genome sequencing.

Background: Universities are facing increased budget constraints, often resulting in reduced funds to support microbiology laboratories. Online mock laboratory activities are often instituted as a cost-effective alternative to traditional wet labs for medical students. Objective: The purpose of this study was to examine students' perceptions of online and in-person microbiology lab learning experiences. Design: We investigated undergraduate medical student perception of the in-person and online microbiology lab experience; 164 first-year medical students participated in newly designed online labs, while 83 second-year medical students continued to use in-person labs. An online survey was administered to collect student opinions of the lab experience. Results: In terms of student self-reported learning styles, those students who attended the lab in person were more likely to report a tactile learning style (33% vs 16%) while those students who learned the material online reported a visual learning style preference (77% vs 61%; n = 264). Students felt that the online microbiology lab was more convenient for their schedules when compared to the in-person lab. A greater proportion of online students (12%) felt that they encountered brand-new material on the final quiz than in-person students (1%; n = 245). Even so, 43% of the online educated students and 37% of the in-person educated students perceived their assigned lab experiences to be the optimal lab design, and over 89% of both groups reported a desire for at least some in-person instruction in a wet-laboratory environment. Conclusions: Our findings suggest that, while students are strongly supportive of digital online lab activities, the overwhelming majority of students still report a desire for a blend of online and in-person, hands-on laboratory activities. These findings will further research directed towards student perception of the lab experience and aid in the adaptation of microbiology curriculums to accommodate both student and university needs.

Hepatitis B virus (HBV) and hepatitis delta virus (HDV) are major sources of acute and chronic hepatitis. HDV requires the envelope proteins of HBV for the processes of assembly and infection of new cells. Both viruses are able to infect hepatocytes though previous studies have failed to determine the mechanism of entry into such cells. This study began with evidence that suramin, a symmetrical hexasulfated napthylurea, could block HDV entry into primary human hepatocytes (PHH) and was then extrapolated to incorporate findings of others that suramin is one of many compounds that can block activation of purinergic receptors. Thus other inhibitors, pyridoxal-phosphate-6-azophenyl-2',4'-disulfonate (PPADS) and brilliant blue G (BBG), both structurally unrelated to suramin, were tested and found to inhibit HDV and HBV infections of PHH. BBG, unlike suramin and PPADS, is known to be more specific for just one purinergic receptor, P2X7. These studies provide the first evidence that purinergic receptor functionality is necessary for virus entry. Furthermore, since P2X7 activation is known to be a major component of inflammatory responses, it is proposed that HDV and HBV attachment to susceptible cells, might also contribute to inflammation in the liver, that is, hepatitis.

Over 150 different proteins attach to the plasma membrane using glycosylphosphatidylinositol (GPI) anchors. Mutations in 18 genes that encode components of GPI-anchor biogenesis result in a phenotypic spectrum that includes learning disability, epilepsy, microcephaly, congenital malformations and mild dysmorphic features. To determine the incidence of GPI-anchor defects, we analysed the exome data from 4293 parent-child trios recruited to the Deciphering Developmental Disorders (DDD) study. All probands recruited had a neurodevelopmental disorder. We searched for variants in 31 genes linked to GPI-anchor biogenesis and detected rare biallelic variants in PGAP3, PIGN, PIGT (n=2), PIGO and PIGL, providing a likely diagnosis for six families. In five families, the variants were in a compound heterozygous configuration while in a consanguineous Afghani kindred, a homozygous c.709G>C; p.(E237Q) variant in PIGT was identified within 10-12 Mb of autozygosity. Validation and segregation analysis was performed using Sanger sequencing. Across the six families, five siblings were available for testing and in all cases variants co-segregated consistent with them being causative. In four families, abnormal alkaline phosphatase results were observed in the direction expected. FACS analysis of knockout HEK293 cells that had been transfected with wild-type or mutant cDNA constructs demonstrated that the variants in PIGN, PIGT and PIGO all led to reduced activity. Splicing assays, performed using leucocyte RNA, showed that a c.336-2A>G variant in PIGL resulted in exon skipping and p.D113fs*2. Our results strengthen recently reported disease associations, suggest that defective GPI-anchor biogenesis may explain ~0.15% of individuals with developmental disorders and highlight the benefits of data sharing.

To finish out the Methodology Corner's focus in 2025 on questionable research practices, attention is called to the problem of HARKing. When research works omit that a finding being reported on and explained was discovered post hoc, a number of unwanted problems can ensue. Several strategies are suggested that might help our community manage the problems associated with HARKing.

The Methodology Corner has opted to call attention to questionable research practices in 2025. This first column of the year specifically looks at p-hacking. Studies subject to p-hacking may be harmful to the science of nursing education. This article provides recommendations for the nursing education community on how to help prevent p-hacking in the nursing literature. [J Nurs Educ. 2025;64(3):211–212.]

In keeping with the focus on questionable research practices in 2025, this entry of the Methodology Corner calls attention to the practice of cherry picking. Studies subject to cherry picking have the potential to introduce inaccurate information into the nurse education literature. This column highlights a few recommendations our community might utilize to help dissuade the practice of cherry picking. [J Nurs Educ. 2025;64(7):467–468.]

A cursory review of relevant research works published in the Journal of Nursing Education suggests our community relies heavily on Cohen's d. Although Cohen's d is a valuable effect size, it possesses a number of limitations that warrants our community adopting a wider set of effect size statistics to help promote a valid science of nursing education. We specifically call attention to Hedges' g. [J Nurs Educ. 2023;62(5):316–317.]