Wellcome Open Research最新文献

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.

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.

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), 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.

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.

We present a genome assembly from an individual Bromus sterilis (the barren brome; Streptophyta; Magnoliopsida; Poales; Poaceae). The genome sequence has a total length of 2,677.90 megabases. Most of the assembly is scaffolded into 7 chromosomal pseudomolecules. The mitochondrial and plastid genome assemblies have lengths of 523.28 kilobases and 136.96 kilobases, respectively. Gene annotation of this assembly on Ensembl identified 29,147 protein-coding genes.

We present a genome assembly from an individual male Myotis mystacinus (whiskered bat; Chordata; Mammalia; Chiroptera; Vespertilionidae). The genome sequence has a total length of 2,081.20 megabases. Most of the assembly (97.52%) is scaffolded into 23 chromosomal pseudomolecules, including the X and Y sex chromosomes. The mitochondrial genome has also been assembled and is 16.93 kilobases in length.

We present a genome assembly from a juvenile female Lagenorhynchus albirostris (the white-beaked dolphin; Chordata; Mammalia; Artiodactyla; Delphinidae). The genome sequence has a total length of 2,544.80 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 16.39 kilobases in length.

Background: Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease caused by mutations in the dystrophin gene. DE50-MD dogs are an animal model of DMD used as a final translational model for evaluation of promising treatments. MicroRNA (miR) expressions in the muscle of DE50-MD dogs represent potential biomarkers, but stable reference miRs must first be identified. The aim of this paper was to establish a panel of reference miRs for WT and DE50-MD dogs over a range of ages and muscle groups.

Methods: RNA was extracted from WT and DE50-MD dog (N=6 per genotype) vastus lateralis muscle samples collected longitudinally at 3, 6, 9, 12, 15 and 18 months of age, and from muscles collected post-mortem (N=3 per genotype; cranial tibial, semimembranosus, lateral triceps and diaphragm). 87 RNAs were quantified in a subset of 6-month-old WT and DE50-MD muscles (N=4 per genotype) using the QIAcuity miFinder panel. GeNorm, BestKeeper and Normfinder were used to identify a candidate panel of the 8 most stable small RNAs, which were then quantified in all RNA samples, alongside the commonly used reference RNA snRNA U6.

Results: The most stable miRs of this subset were used to normalise quantities of dystromiRs miR-1, miR-133a and miR-206, and fibromiR miR-214. MicroRNAs miR-191, let-7b, miR-125a and miR-15a were the most stable miRs tested, while snRNA U6 performed poorly. DystromiR expression, normalised to the geometric mean of the panel of reference miRs, was lower for miR-1 and miR-133a in DE50-MD compared to WT muscles, while miR-206 levels did not significantly differ between genotypes. FibromiR miR-214 was 2- to 4-fold higher in DE50-MD versus WT muscles.

Conclusions: A normalisation factor derived from miR-191, let-7b, miR-125a and miR-15a is suitable for normalising miR expression data from WT and DE50-MD muscle over a range of ages and muscle types.