Wellcome Open Research最新文献

We present a genome assembly from an individual female specimen of Ostrinia nubilalis (European Corn Borer; Arthropoda; Insecta; Lepidoptera; Crambidae). The genome sequence has a total length of 495.50 megabases. Most of the assembly (99.87%) is scaffolded into 32 chromosomal pseudomolecules, including the Z and W sex chromosomes. The mitochondrial genome has also been assembled and is 15.24 kilobases in length. Gene annotation of this assembly on Ensembl identified 16,780 protein-coding genes.

Background: This study aimed to assess the current status of critical care services in 13 districts of Bagmati Province in Nepal, with a focus on access, infrastructure, human resources, and intensive care unit (ICU) services.

Methods: A cross-sectional survey was conducted among healthcare workers employed in 87 hospitals having medical/surgical ICUs across Bagmati Province. Data were collected through structured questionnaires administered via face-to-face and telephone survey. Descriptive analysis was used for data analysis, involving frequencies and percentages.

Results: From 87 hospitals, a total of 123 ICUs were identified in the province, providing 1167 beds and 615 functioning ventilators. The average ICU bed availability per 100,000 population was 19, ranging from 3.6 in Makwanpur to 33.9 in Kathmandu. Out of 13 districts, 95% of beds were concentrated in just four districts, while six had no ICU facilities. Of the available facilities, 69.9% were owned by private entities. One-to-one nurse-to-ventilated bed ratio was maintained by 63.4% of ICUs during daytime, and 62.6% at nighttime. Furthermore, 74.8% of ICUs had consultants trained in critical care medicine. While essential equipment availability was higher in Bagmati province, gaps existed in the availability of oxygen plants and isolation rooms. Similarly, many ICUs offered continuous medical education and cardiopulmonary resuscitation (CPR) training, but improvements were necessary in clinical audits, antibiotic stewardship programs, and research engagement.

Conclusions: Disparities in critical care resources were evident across districts in Bagmati Province, highlighting the need for a balanced and decentralized approach to ensure equitable access to care. Although there were disparities, numerous ICUs were effectively carrying out multiple critical care procedures. This study suggests conducting a nationwide mapping of ICU resources, prioritizing infrastructure development, optimizing resource allocation, and establishing national protocols.

The increasing threat from infection with drug-resistant pathogens is among the most serious public health challenges of our time. Formed by Wellcome in 2018, the Surveillance and Epidemiology of Drug-Resistant Infections Consortium (SEDRIC) is an international think tank whose aim is to inform policy and change the way countries track, share, and analyse data relating to drug-resistant infections, by defining knowledge gaps and identifying barriers to the delivery of global surveillance. SEDRIC delivers its aims through discussions and analyses by world-leading scientists that result in recommendations and advocacy to Wellcome and others. As a result, SEDRIC has made key contributions in furthering global and national actions. Here, we look back at the work of the consortium between 2018-2024, highlighting notable successes. We provide specific examples where technical analyses and recommendations have helped to inform policy and funding priorities that will have real-world impact on the surveillance and epidemiology of infections with drug-resistant pathogens.

Despite significant investment in High-Performance Computing (HPC) clusters by funding councils, there are still many researchers whose workflows could not benefit from the computation speed that is provided by these clusters. Reducing barriers to entry for these researchers would accelerate their scientific throughput, since they will be able to respond to results in a timely fashion, improving either their protocols or correcting any problems that might have arisen. This improves the quality of science, and therefore the return on investment, in computationally-intensive areas such as Cryogenic Electron Microscopy (cryo-EM). This paper outlines a technique, FlowCron, for users to analyse their data on a HPC facility with minimal training, increasing accessibility. FlowCron transfers the responsibilities of installation and upkeep of data processing pipelines from users to HPC systems administrators, simplifies the set up of HPC pipelines, and makes pipelines as reliable as possible once set up. The work described here has software dependencies that are common to the majority of HPC clusters. We achieve this by linking Globus and cron to produce an open-source system that requires little administrative support but provides a very easy way of running an analysis on a HPC system. The user starts the analysis through the Globus website and, when started, the data will be encrypted, uploaded to the HPC, analysed, and returned to the originating machine, along with a record of the analysis.

Background: There is limited knowledge regarding African genetic drivers of disease due to prohibitive costs of large-scale genomic research in Africa.

Methods: We piloted a scalable virtual genotyped cohort in South Africa that was affordable in this resource-limited context, cost-effective, scalable virtual genotyped cohort in South Africa, with participant recruitment using a tiered informed consent model and DNA collection by buccal swab. Genotype data was generated using the H3Africa Illumina micro-array, and phenotype data was derived from routine health data of participants. We demonstrated feasibility of nested case control genome wide association studies using these data for phenotypes type 2 diabetes mellitus (T2DM) and severe COVID-19.

Results: 2267346 variants were analysed in 459 participant samples, of which 229 (66.8%) are female. 78.6% of SNPs and 74% of samples passed quality control (QC). Principal component analysis showed extensive ancestry admixture in study participants. Of the 343 samples that passed QC, 93 participants had T2DM and 63 had severe COVID-19. For 1780 previously published COVID-19-associated variants, 3 SNPs in the pre-imputation data and 23 SNPS in the imputed data were significantly associated with severe COVID-19 cases compared to controls (p<0.05). For 2755 published T2DM associated variants, 69 SNPs in the pre-imputation data and 419 SNPs in the imputed data were significantly associated with T2DM cases when compared to controls (p<0.05).

Conclusions: The results shown here are illustrative of what will be possible as the cohort expands in the future. Here we demonstrate the feasibility of this approach, recognising that the findings presented here are preliminary and require further validation once we have a sufficient sample size to improve statistical significance of findings.We implemented a genotyped population cohort with virtual follow up data in a resource-constrained African environment, demonstrating feasibility for scale up and novel health discoveries through nested case-control studies.

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.