Wellcome Open Research最新文献

Tuberculous meningitis (TBM) is the most severe form of tuberculosis. Corticosteroids are currently recommended as an adjunctive therapy in HIV-negative adults with TBM. However, benefit from corticosteroids in TBM may depend upon host leukotriene A4 hydrolase ( LTA4H) genotype and the corresponding inflammatory phenotypes. This article describes the planned analyses for the primary publication of the results of the LAST ACT clinical trial (NCT03100786): 'Leukotriene A4 hydrolase Stratified Trial of Adjunctive Corticosteroids for HIV-negative adults with Tuberculous meningitis'. The primary hypothesis addressed by the trial is that LTA4H genotype, in particular CC or CT genotype, determines whether adjunctive dexamethasone benefits or harms adults with TBM. The trial was an LTA4H genotype stratified, parallel group, randomised, double blind, placebo-controlled multi-centre Phase III trial of dexamethasone given for 6-8 weeks in addition to standard anti-tuberculosis drugs. LTA4H genotype (CC, CT, TT) was determined in all participants prior to randomisation; only those with CC or CT genotype were randomised to dexamethasone or placebo. All TT genotype participants received dexamethasone because prior data indicated survival was increased by dexamethasone in this genotype. The primary endpoint was all-cause death or new neurological event over the first 12 months after randomisation. We took a hybrid trial-design approach which aims to prove non-inferiority of placebo first but also allows claiming superiority of placebo in case dexamethasone causes substantial harm. This statistical analysis plan expands upon and updates the analysis plan outlined in the published study protocol.

We present a genome assembly from a male specimen of Perizoma flavofasciatum (Sandy Carpet; Arthropoda; Insecta; Lepidoptera; Geometridae). The genome sequence has a total length of 369.30 megabases. Most of the assembly (99.88%) is scaffolded into 30 chromosomal pseudomolecules, including the Z sex chromosome. The mitochondrial genome has also been assembled and is 16.61 kilobases in length. Gene annotation of this assembly on Ensembl identified 11,915 protein-coding genes.

We present a genome assembly from an individual female Panstrongylus geniculatus (kissing bug; Arthropoda; Insecta; Hemiptera; Reduviidae). The assembly contains two haplotypes with total lengths of 1,362.73 megabases and 1,342.40 megabases, respectively. Most of haplotype 1 (97.5%) is scaffolded into 12 chromosomal pseudomolecules. Haplotype 2 is assembled to scaffold level. The mitochondrial genome has also been assembled and is 17.44 kilobases in length.

We present a genome assembly from an individual female specimen of Catocala nupta (Red Underwing; Arthropoda; Insecta; Lepidoptera; Erebidae). The genome sequence has a total length of 930.40 megabases. Most of the assembly (99.82%) is scaffolded into 32 chromosomal pseudomolecules, including the W and Z sex chromosomes. The mitochondrial genome has also been assembled and is 15.57 kilobases in length. Gene annotation of this assembly on Ensembl identified 13,889 protein-coding genes.

Background: The skeletal muscle has mainly a structural function and plays a role in human's metabolism. Besides, the association between sleep quality and muscle mass, in the form of sarcopenia, has been reported. This study aimed to assess whether changes of skeletal muscle mass (SMM) over time are associated with baseline sleep duration and disturbances in a resource-constrained adult Peruvian population.

Materials and methods: Secondary analysis using information of a population-based intervention. The outcome was SMM assessed using bioimpedance and the second version of the Lee's formula. The exposures were baseline self-reported sleep duration (normal, short and long sleepers) and disturbances (sleep difficulties and awakening at nights). Crude and adjusted linear mixed models were used to assess the associations of interest, and coefficients (β) and 95% confidence intervales (95% CI) were reported.

Results: Data from 2,310 individuals at baseline, mean age 43.4 (SD: 17.2), and 1,163 (50.4%) females were analyzed. Sleep duration was 7.8 (SD: 1.3) hours/day, with 15.3% short sleepers and 11.6% long sleepers, whereas 24.2% reported sleep difficulties and 25.1% awakening at nights. In multivariable model, SMM among short and long sleepers did not vary significantly over time using the Lee's formula; however, SMM was lower at the end of follow-up for long sleepers using bioimpedance (-0.26 kg; 95% CI: -0.47 to -0.06). Sleep disturbances were associated with a gradual SMM reduction: 0.36 kg using bioimpedance and 0.25 kg using the formula at the end of follow-up.

Conclusions: Using bioimpedance and formula estimations, sleep disturbances were associated with a reduction of SMM over a period of 2.4 years. Regarding sleep duration, no SMM changes over time were seen in short sleepers, but findings were discordant in long sleepers: a reduction of SMM using bioimpedance, but no change using the formula.

We present a genome assembly from an individual male Dolichopus griseipennis (Arthropoda; Insecta; Diptera; Dolichopodidae). The genome sequence has a total length of 897.50 megabases. Most of the assembly is scaffolded into 6 chromosomal pseudomolecules, including the X sex chromosome. The mitochondrial genome has also been assembled and is 16.12 kilobases in length. Gene annotation of this assembly on Ensembl identified 12,532 protein-coding genes.

Background: Dementia prevalence in low- and middle-income countries is increasing, yet epidemiological data from African populations remain scarce. Crucial risk factors differ in Africa from more intensively studied global areas, including a higher burden of cerebrovascular disease and HIV, but lower rates of other risk factors like physical inactivity.Understanding dementia aetiology in African settings has been limited by the expensive and invasive nature of biomarker testing. This study leverages developments in blood-based and retinal imaging biomarker technology to examine the drivers of dementia in older Ugandans.People with dementia have complex needs benefiting from multi-dimensional support. Understanding current services will allow identification of barriers and opportunities to strengthen support available to people with dementia and their families.

Methods: The study is nested within the General Population Cohort run by the Medical Research Council/Uganda Virus Research Institute & London School of Hygiene and Tropical Medicine Research Unit. All adults aged 60+ (around 1400) are undergoing brief cognitive screening.In Part 1, cohort participants are selected based on screening scores to undergo detailed cognitive assessment, using methods developed by the 10/66 Dementia Research Group. Part 2 is a case control study of people with and without dementia using antecedent data, questionnaires, physical assessment, retinal imaging, and Alzheimer's blood-based biomarkers. We will also compare disability, frailty, quality of life, and social engagement in people with and without dementia.Part 3 assesses current formal support structures for people with dementia through review of publicly available literature and expert interviews.

Conclusions: This is the first study in Africa using blood-based and retinal imaging biomarkers to examine pathological processes underlying dementia, and systematically map services available for people with dementia. This paves the way for effective policy strategies and further focused research regarding both dementia prevention and support for affected people and their families.

We present a genome assembly from an individual female Solea solea (Linnaeus, 1758) (the common sole; Chordata; Actinopteri; Pleuronectiformes; Soleidae). The genome sequence spans 643.80 megabases. Most of the assembly (97.81%) is scaffolded into 21 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 17.03 kilobases in length. Gene annotation of this assembly on Ensembl identified 21,646 protein-coding genes.

We present a genome assembly from a female specimen of Athalia cordata (sawfly; Arthropoda; Insecta; Hymenoptera; Athaliidae). The genome sequence has a total length of 169.00 megabases. Most of the assembly (99.98%) is scaffolded into 4 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 27.47 kilobases in length.

We present a genome assembly from a specimen of Diogma glabrata (cranefly; Arthropoda; Insecta; Diptera; Cylindrotomidae). The genome sequence has a total length of 1,328.70 megabases. Most of the assembly (90.7%) is scaffolded into 4 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 17.5 kilobases in length.