Wellcome Open Research最新文献

We present a genome assembly from an individual female Balaenoptera acutorostrata (the minke whale; Chordata; Mammalia; Artiodactyla; Balaenopteridae). The genome sequence has a total length of 2,772.90 megabases. Most of the assembly is scaffolded into 22 chromosomal pseudomolecules, including the X sex chromosome. The mitochondrial genome has also been assembled and is 16.42 kilobases in length.

Background: Burkholderia thailandensis is an environmental bacteria closely related to Burkholderia pseudomallei that rarely causes infection in humans. Some environmental isolates have shown to express a capsular polysaccharide known as B. thailandensis capsular variant (BTCV), but human infection has not previously been reported. Although B. thailandenisis has been identified in environmental samples in Laos before, there have not been any human cases reported.

Case: A 44-year-old man presented to a district hospital in Laos with a short history of fever and pain in his left foot. Physical examination identified a deep soft-tissue abscess in his left foot and an elevated white blood count. A deep pus sample was taken and melioidosis was suspected from preliminary laboratory tests. The patient was initially started on cloxacillin, ceftriaxone and metronidazole, and was then changed to ceftazidime treatment following local melioidosis treatment guidelines.

Laboratory methods: A deep pus sample was sent to Mahosot Hospital microbiology laboratory where a mixed infection was identified including Burkholderia sp. Conventional identification tests and API 20NE were inconclusive, and the B. pseudomallei-specific latex agglutination was positive. The isolate then underwent a Burkholderia species specific PCR which identified the isolate as B. thailandensis. The isolate was sent for sequencing on the Illumina NovaSeq 6000 system and multi-locus sequence typing analysis identified the isolate had the same sequence type (ST696) as B. thailandensis E555, a strain which expresses a B. pseudomallei-like capsular polysaccharide.

Conclusion: This is the first report of human infection with B. thailandensis in Laos, and the first report of any human infection with the B. thailandensis capsular variant. Due to the potential for laboratory tests to incorrectly identify this bacteria, staff in endemic areas for B. thailandensis and B. pseudomallei should be aware and ensure that appropriate confirmatory methods are used to differentiate between the species.

We present a genome assembly from an individual female Harmonia axyridis (the harlequin ladybird; Arthropoda; Insecta; Coleoptera; Coccinellidae). The genome sequence is 426 megabases in span. The majority (99.98%) of the assembly is scaffolded into 8 chromosomal pseudomolecules, with the X sex chromosome assembled.

Background: Research undertaken using the Born in Bradford cohort study identified consanguinity as a major risk factor for congenital anomalies and also reported longer term adverse health outcomes associated with consanguinity.

Methods: We report the prevalence of consanguinity from two cohort studies in the same geographical area with a nine year gap: Born in Bradford (BiB) and Born in Bradford's Better Start (BiBBS). We examine and compare rates of consanguinity and the characteristics of the consanguineous in each study population to examine if and how these have changed in the years between the recruitment periods of 2007-2010 (BiB) and 2016-2019 (BiBBS).

Results: There had been a substantial decrease in consanguineous unions in women of Pakistani heritage, the proportion of women who were first cousins with the father of their baby fell from 39.3% to 27.0%, and those who were other blood relations fell from 23.1% to 19.3%. Only 37.6% of Pakistani heritage women were unrelated to the father of their baby in BiB, but 53.7% were unrelated in BiBBS. All but one White British respondent was unrelated to their baby's father in both cohorts, and around 90% of the 'Other ethnicities' group (i.e., not White British or Pakistani heritage) were unrelated to the baby's father in both cohorts. The reduction was most marked in women of Pakistani heritage who were born in the UK, in those educated to A level or higher and in women under age 25.

Conclusions: An appreciation of changing rates of consanguinity and linked health needs will be valuable to those who commission and provide antenatal, paediatric and genetic services in Bradford and in other areas where consanguinity is likely to be a major risk factor. Falling rates in this city may reflect wider changes in partner choices in similar populations.

We present a genome assembly from an individual male Subacronicta megacephala (Poplar Grey moth; Arthropoda; Insecta; Lepidoptera; Noctuidae). The genome sequence has a total length of 424.20 megabases. Most of the assembly (99.02%) is scaffolded into 31 chromosomal pseudomolecules, including the Z sex chromosome. The mitochondrial genome has also been assembled and is 15.35 kilobases in length. Gene annotation of this assembly on Ensembl identified 18,189 protein-coding genes.

Background: Binary diagnostic tests are commonly used in medicine to answer a question about a patient's clinical status, most commonly, do they or do they not have some disease. Recent advances in statistical methodologies for performing inferential statistics to compare commonly used test metrics for two diagnostic tests have not yet been implemented in a statistical package.

Methods: Up-to-date statistical methods to compare the test metrics achieved by two binary diagnostic tests are implemented in the new R package testCompareR. The output and efficiency of testCompareR is compared to the only other available package which performs this function, DTComPair, as well as an open-source program, compbdt, using a motivating example.

Results: testCompareR achieves similar results to DTComPair using statistical methods with improved coverage and asymptotic performance. Further, testCompareR is faster than the currently available package and requires fewer pre-processing steps in order to produce accurate results.

Conclusions: testCompareR provides a new tool to compare the test metrics for two binary diagnostic tests compared with the gold standard. This tool allows flexible inputs, which minimises the need for data pre-processing, and operates in very few steps, so that it is easy to use even for those less experienced with R. testCompareR achieves results comparable to those computed by DTComPair, using optimised statistical methods and with improved computational efficiency.

Introduction: The World Health Organization global antimicrobial resistance surveillance system (GLASS) was rolled out in 2015 to guide antimicrobial resistance (AMR) surveillance. However, its implementation in Africa has not been fully evaluated. We conducted a scoping review to establish the progress of implementing the WHO 2015 GLASS manual in Africa.

Methods: We used MeSH terms to comprehensively search electronic databases (MEDLINE and Embase) for articles from Africa published in English between January 2016 and December 2023. The Arksey and O'Malley's methodological framework for scoping reviews was employed. Data were collected on compliance with WHO GLASS recommendations for AMR surveillance-priority samples, pathogens, and pathogen-antibiotic combinations and analysed using Microsoft Excel.

Results: Overall, 13,185 articles were identified. 7,409 were duplicates, and 5,141 articles were excluded based on titles and abstracts. 609 full-text articles were reviewed, and 147 were selected for data extraction. Of the 147 selected articles, 78.9% had been published between 2020 and 2023; 57.8% were from Eastern Africa. 93.9% of articles were on cross-sectional studies. 96.6% included only one priority sample type; blood (n=56), urine (n=64), and stool (n=22). Of the 60 articles that focused on blood as a priority sample type, 71.7%, 68.3%, 68.3%, 36.7%, 30%, and 10% reported recovery of Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Salmonella species and Streptococcus pneumoniae, respectively. Salmonella and Shigella species were reported to have been recovered from 91.3% and 73.9% of the 23 articles that focused on stool. E. coli and K. pneumoniae recoveries were also reported from 94.2% and 68.1% of the 69 articles that focused on urine. No article in this review reported having tested all the recommended WHO GLASS pathogen-antibiotic combinations for specific pathogens.

Conclusion: Progress has been made in implementing the GLASS recommendations in Africa, but adoption varies across countries limiting standardisation and comparability of data.

Background: Infection during pregnancy with SARS-CoV-2 can have a serious impact on both maternal and foetal health. Clinical studies have shown that SARS-CoV-2 transmission from the mother to the foetus typically does not occur. However, there is evidence that SARS-CoV-2 can infect the placenta in utero. Here we sought to quantify the permissiveness of placental cells to SARS-CoV-2 infection and to determine if they support viral release.

Methods: By using publicly available single-cell RNA sequencing (scRNAseq) data sets and confocal microscopy we compared ACE2 transcript and protein expression across human first trimester and term placental cells. We also used in vitro infection assays to quantify the infection rates of a range of placenta-derived cells. Finally, we quantified the viral egress from these cells.

Results: ACE2 transcripts are found in a range of placental cell types across gestation, including trophoblast. However, ACE2 protein expression does not significantly change across placental cell types from first trimester to term. We find that 0.5±0.15 % of term trophoblast cells can be infected with SARS-CoV-2 while primary placental fibroblasts and macrophages, and JEG-3, JAR and HUVEC cell lines are resistant to infection. Furthermore, primary trophoblast cells poorly support viral release while JEG-3 cells allow relatively high levels of viral release.

Conclusions: The low level of viral release by primary placental cells provides insight into how the virus is impaired from crossing the placenta to the foetus.

Background: Over 250 million children are developing sub-optimally due to their exposure to early life adversities. While previous studies have examined the independent effects of nutritional status, psychosocial adversities, and environmental pollutants on children's outcomes, little is known about their interaction and cumulative effects.

Objectives: This study aims to investigate the independent, interaction, and cumulative effects of nutritional, psychosocial, and environmental factors on children's cognitive development and mental health in urban and rural India. It also seeks to explain pathways leading to inequities in child outcomes at the individual, household, and neighbourhood levels.

Methods: A mixed-methods prospective cohort study will be conducted on 1600 caregiver-child dyads (child age 3-10 years) in urban and rural India. Nutritional status, psychosocial adversities, environmental pollutants, and child mental health outcomes will be assessed using parent-report questionnaires. Performance-based measures will be used to assess cognitive outcomes. Venous blood and urine samples will be used to measure nutritional and pesticide biomarkers in 500 children. Indoor air pollution will be monitored in 200 households twice, during two seasons. Multilevel regression, weighted quantile sum regression, and Bayesian kernel machine regression will assess the individual and combined effects of exposures on child outcomes. Thematic analysis of in-depth interviews and focus group discussions will explore pathways to middle-and late childhood development inequities.

Discussion: The data will be used to formulate a Theory of Change (ToC) to explain the biological, psychosocial, and environmental origins of children's cognitive and mental health outcomes across the first decade of life in diverse Indian settings, which can inform interventions targets for promoting children's outcomes beyond the first 1000 days, potentially generalizable to similar under-resourced global settings. The COINCIDE research infrastructure will comprise a valuable global health resource, including prospective cohort data, validated study tools, and stored biological and environmental samples for future studies.

Background: Novel host-directed therapies are urgently needed for patients with dengue, particularly those at high risk of developing severe disease. Broad immunosuppression using corticosteroids in unselected patients with dengue has so far been unsuccessful. Patients with hyperinflammation (raised CRP and/or ferritin levels) are at highest risk of poor outcomes in dengue. Anakinra is a licensed, bio-engineered form of the naturally occurring IL-1R antagonist which has shown efficacy in other acute viral-associated hyperinflammatory syndromes.

Methods: This is a randomized placebo-controlled phase II trial of anakinra in 160 patients ≥ 12 years old, diagnosed as having dengue with warning signs or severe dengue and the hyperinflammatory syndrome (plasma ferritin >2000 ng/ml). Participants will receive a 4-day course of either anakinra or placebo. The primary endpoint is the efficacy of anakinra measured by the delta mSOFA score* (change in mSOFA score over 4 days after randomization). The accompanying immunological and transcriptomic analyses aim to identify novel mechanisms and pathways that may represent future biomarkers and therapeutic targets.

Discussion: The observed immunomodulatory benefit of anakinra in acute viral-associated hyperinflammatory syndromes including COVID-19 and auto-immune diseases makes this medication a promising potential treatment for dengue patients with hyperinflammation. This trial will assess the safety and efficacy of anakinra in patients with severe dengue or at high risk of developing life-threatening dengue disease.

Registration: ClinicalTrials.gov (NCT05611710).