Wellcome Open Research最新文献

We present a genome assembly from a specimen of Opisthorchis viverrini (liver fluke; Platyhelminthes; Trematoda; Opisthorchiida; Opisthorchiidae). The genome sequence has a total length of 627.20 megabases. Most of the assembly (97.89%) is scaffolded into 6 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 18.04 kilobases in length.

We present a genome assembly from an individual male specimen of Abia candens (sawfly; Arthropoda; Insecta; Hymenoptera; Cimbicidae). The genome sequence has a total length of 261.00 megabases. Most of the assembly (82.7%) is scaffolded into 16 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 19.72 kilobases in length.

Background: Dehydration secondary to diarrhoea is a major cause of hospitalization and mortality in children aged less than five years. Most diarrhoea cases in childhood are caused by rotavirus, and routine introduction of rotavirus vaccine is expected to reduce the incidence and severity of dehydration secondary to diarrhoea in vaccinated infants. Previously, studies have examined changes in admissions with stools positive for rotavirus but this study reports on all admissions with dehydration secondary to diarrhoea regardless of stool rotavirus results. We aimed to assess the changes in all-cause severe diarrhoea and dehydration (DAD) admissions following the vaccine's introduction.

Methods: We examined changes in admissions of all clinical cases of DAD before and after introduction of routine vaccination with rotavirus vaccine in July 2014 in Kenya. We use data from 13 public hospitals currently involved in a clinical network, the Clinical Information Network (CIN). Routinely collected data for children aged 2-36 months were examined. We used a segmented mixed effects model to assess changes in the burden of diarrhoea and dehydration after introduction of rotavirus vaccine. For sensitivity analysis, we examined trends for non-febrile admissions (surgical or burns).

Results: There were 17,708 patients classified as having both diarrhoea and dehydration. Average monthly admissions due to DAD for each hospital before vaccine introduction (July 2014) was 35 (standard deviation: ±22) and 17 (standard deviation: ±12) after vaccine introduction. Segmented mixed effects regression model showed there was a 33% (95% CI, 30% to 38%) decrease in DAD admissions immediately after the vaccine was introduced to the Kenya immunization program in July 2014. There was no change in admissions due to non-febrile admissions pre-and post-vaccine introduction.

Conclusion: The rotavirus vaccine, after introduction into the Kenya routine immunization program resulted in reduction of all-cause admissions of diarrhoea and dehydration in children to public hospitals.

Background: Yellow fever (YF) is a mosquito-borne and recently re-emerging viral haemorrhagic fever endemic to sub-Saharan Africa and South America. A highly effective vaccine against YF is licensed and recommended as part of routine childhood immunisation as a single dose at 9 months. Recent observational data demonstrate waning immunity following single primary vaccination and suggest that children in endemic areas may require booster vaccination.

Methods: This open-label, non-randomised clinical vaccine trial (ClinicalTrials.gov, NCT05332197, registered on 31 March 2022, URL: https://clinicaltrials.gov/study/NCT05332197) will assess the safety and immunogenicity of a booster dose of the licensed 17D YF vaccine in Gambian children. The trial will recruit 750 children in three cohorts of different ages (250 each). All children were vaccinated with the 17D YF vaccine at 9-10 months of age as part of clinical trials run by the Medical Research Council (MRC) Unit The Gambia, and are thus well-characterised, including basic clinical, anthropometric, and post-primary immunogenicity data. The children will receive booster doses at 15 months, 4 years, or 8.5 years. Serum samples will be taken before and 28 days after the booster, with additional sampling for exploratory endpoints in subgroups. Adverse events are solicited for the first three days following vaccination and recorded throughout the study period. The primary objective of the trial is to describe the safety and immunogenicity of the booster in the different age cohorts. Secondary objectives are to characterise the rate of sero-reversion (change from seropositive to seronegative) over a period of 9 months to 8 years following single primary vaccination and to profile the immune response to the booster to explore underlying mechanisms for the longevity of vaccine-induced antibody.

Discussion: The results of this trial are likely to directly impact WHO recommendations on whether booster vaccination is required for children in endemic areas, and if so, the optimal timing of such a booster.

Background: Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are patterns of kidney injury observed in the filtering units of the kidney known as glomeruli. These histological patterns are seen in kidney biopsies from individuals with idiopathic nephrotic syndrome (iNS), which occurs in both children and adults. However, there is some indication that MCD and FSGS are within the same phenotypic spectrum.

Methods: From the NURTuRE cohort of individuals with NS, we performed laser microdissection and mass spectrometry analysis of kidney biopsy samples to identify proteomic patterns of disease. 56 individuals with iNS segregated by histological pattern (37 MCD and 19 FSGS) across three age groups: early childhood (0-6 years), late childhood (6-18 years) and adult (>18 years).

Results: We found no distinct clustering of proteomic profiles between MCD and FSGS, but identified global differences in glomerular cell and extracellular matrix composition related to both histological pattern and age. The proteomic data are available via ProteomeXchange with identifier PXD053362.

Conclusions: The lack of distinct clustering between MCD and FSGS in our study suggests shared biological processes between these injury patterns of iNS, supporting the hypothesis that they are part of the same disease spectrum. The global differences observed in glomerular cell and extracellular matrix composition suggest involvement of diverse biogeological processes as different patterns of iNS manifests in different age groups. This study also demonstrates the feasibility of pooling bioresources, central processing of heterogeneous tissue samples, and developing laser-microdissection and proteomic analysis methodology.

Background: Periodontitis, one of the most common forms of periodontal disease, has been linked to several cardiovascular factors including metabolic syndrome and inflammatory processes. This study aimed to determine the association between type 2 diabetes mellitus (T2DM) and periodontitis in a representative sample of individuals in the north of Peru.

Materials and methods: Secondary data analysis using information of a population-based survey, enrolling subjects aged 35 to 69 years. The outcome was periodontitis, evaluated using a self-reported and validated 8-item questionnaire (≥5 points compatible with severe periodontitis compared to those without severe periodontitis), whereas the exposure was the presence of T2DM, evaluated using results of oral glucose tolerance test and categorized into two different forms: (a) normoglycemic, prediabetes, and T2DM, and (b) without T2DM, with T2DM and <5 years of diagnosis, and with T2DM and ≥5 years of diagnosis. Poisson regression models were utilized to report prevalence ratios (PR) and 95% confidence intervals (95% CI).

Results: Data from 1606 individuals were analyzed, with a mean age of 48.2 (SD: 10.6) years, and 50.3% were women. Of these, 272 (16.9%) had prediabetes and 176 (11.0%) had T2DM (71.6% with <5 years of disease). Overall, 97.0% presented at least one symptom compatible with periodontitis, 882 (55.0%) had mild, 643 (40.0%) had moderate, and 5% had severe periodontitis. In multivariable model, those with T2DM had a higher prevalence of severe periodontitis (PR = 1.99; 95% CI: 1.12 - 3.54). Similarly, those with <5 years of disease had a higher prevalence of severe periodontitis (PR = 2.48; 95% CI: 1.38 - 4.46).

Conclusions: Our research confirms the association between T2DM and severe periodontitis, especially among those with recent diagnosis (<5 years). Symptoms of periodontitis are quite common in our study population. Our results suggest a need to periodically assess oral health in patients with T2DM.

The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective birth cohort. Since its inception in the early 1990s, the study has collected over thirty years of data on approximately 15,000 mothers, their partners, and their offspring, resulting in over 100,000 phenotype variables to date. Maintaining data security and participant anonymity and confidentiality are key principles for the study, meaning that data access is restricted to bona fide researchers who must apply to use data, which is then shared on a project-by-project basis. Despite these legitimate reasons for restricting data access, this does run counter to emerging best scientific practices encouraging making data openly available to facilitate transparent and reproducible research. Given the rich nature of the resource, ALSPAC data are also a valuable educational tool, used for teaching a variety of methods, such as longitudinal modelling and approaches to modelling missing data. To support these efforts and to overcome the restrictions in place with the study's data sharing policy, we discuss methods for generating and making openly available synthesised ALSPAC datasets; these synthesised datasets are modelled on the original ALSPAC data, thus maintaining variable distributions and relations among variables (including missing data) as closely as possible, while at the same time preserving participant anonymity and confidentiality. We discuss how ALSPAC data can be synthesised using the 'synthpop' package in the R statistical programming language (including an applied example), present a list of guidelines for researchers wishing to release such synthesised ALSPAC data to follow, and demonstrate how this approach can be used as an educational tool to illustrate longitudinal modelling methods.

Venous thromboembolism (VTE) is a common cause of morbidity and mortality in patients with cancer. There is evidence that specific aberrations in tumour biology contribute to the pathophysiology of this condition. We plan to examine the association between tumour somatic mutations and VTE in an existing cohort of patients with cancer, who were enrolled to the flagship Genomics England 100,000 Genomes Project. Here, we outline an a-priori analysis plan to address this objective, including details on study cohort selection, exposure and outcome definitions, annotation of genetic variants and planned statistical analyses. We will assess the effect of 1) deleterious somatic DNA variants in each gene; 2) tumour mutational burden and 3) tumour mutational signatures on the rate of VTE (outcome) in a pan-cancer cohort. Sensitivity analyses will be performed to examine the robustness of any associations, including adjustment for potentially correlated co-variates: tumour type, stage and systemic anti-cancer therapy. We hope that results from this study may help to identify key genes which are implicated in the development of cancer associated thrombosis, which may shed light on related mechanistic pathways and/or provide data which can be integrated into genetic risk prediction models for these patients.

We present a genome assembly from an individual male Stenella coeruleoalba (the striped dolphin; Chordata; Mammalia; Artiodactyla; Delphinidae). The genome sequence has a total length of 2,691.40 megabases. Most of the assembly is scaffolded into 23 chromosomal pseudomolecules, including the X and Y sex chromosomes. The mitochondrial genome has also been assembled and is 16.39 kilobases in length.

Background: In 2021 we launched the BronchStart study, which collected information on 17,899 presentations in children with serious respiratory tract infections following the release of lockdown restrictions. Our study informed the Joint Committee on Vaccination and Immunisation's decision to recommend the introduction maternal respiratory syncytial virus (RSV) vaccination, which was introduced in the United Kingdom in August/September 2024.

Study question: We modified our original protocol to conduct a United Kingdom-wide assessment of maternal vaccination against RSV.

Methods and likely impact: We will conduct a multi-centre study, utilising the PERUKI network used in the original BronchStart study, to assess the effectiveness of maternal vaccination using a test-negative study design. We will gather detailed clinical information on children admitted with bronchiolitis in the post-RSV vaccination era, and understand possible reasons for incomplete vaccine uptake.