Wellcome Open Research最新文献

The objectives of this integrative systematic review were to describe how community researchers (CRs) in low-and middle-income country (LMIC) settings are recruited, trained and supported in research projects, to identify facilitators, challenges and impacts of involving CRs, and to explore CRs' own experiences of conducting research. This area has not previously been synthesised across studies, thereby offering an original contribution to the evidence base. Primary research studies, of any study design and in any language, that provided insights into the review objectives in LMICs were included in the review. Search strategies included database searches and backward and forward chaining. Seven databases were searched on 5th November 2024 without date or language limits: Medline, Embase, CINAHL, PsycINFO, SocINDEX, Web of Science and Global Index Medicus. Quality assessment of included studies was conducted using the Mixed-Methods Appraisal Tool (MMAT). Qualitative synthesis of the findings was undertaken using a reflexive thematic approach. Overall, 39 papers reporting 27 studies were included in the review, with only seven papers scoring under 80% on the MMAT. Findings were synthesised over four themes: (1) recruitment, engagement and support; (2) benefits and challenges to the community researchers and communities; (3) benefits and challenges to the research; (4) ethics of engagement. Engaging CRs offers clear benefits, including improved access to marginalised groups, reduced power imbalances, and richer, culturally informed data. However, this review also highlights ethical concerns, emotional strain, and inequitable compensation, particularly in LMIC contexts where there are structural inequalities, limited resources, and sociocultural challenges. These findings highlight the need for research teams to adopt more ethical and inclusive approaches to CR involvement. Priorities include attribute-based recruitment processes, comprehensive training and ongoing support, fair remuneration, and structures that protect CRs' wellbeing. Strengthening these practices is essential to minimise harm, enhance data quality, and ensure community-engaged research delivers meaningful and equitable benefits.

Background: Patient and public involvement and engagement (PPIE) in research is a collaboration between researchers, patients, and the public, enhancing research acceptability, relevance, and impact. There is a growing prevalence of PPIE in high-income country research; however, its integration in low- and middle-income countries (LMICs) remains poorly understood. Recognising this gap, the Ziauddin University Clinical Trials Unit in Karachi, Pakistan, launched a dedicated PPIE initiative in 2022. This study evaluates the engagement process and experiences of patient and public members and researchers to identify barriers and facilitators to participation within the PPIE group.

Methods: The evaluation uses an explanatory sequential mixed-method design. First, the Public and Patient Engagement Evaluation Tool (PPEET) questionnaire will be administered online to group members, coordinators, and senior institutional leads. Insights from questionnaires will be further explored during semi-structured interviews, with questions guided by the Patient Engagement in Research (PEIR) framework, supplemented with analysis of project documentation. Study activities will be conducted in both English and Urdu. The study has been co-designed with PPIE members and is co-led with a public partner. Findings will highlight areas for improvement, inform best practices, and guide the development of more effective engagement strategies.

Outcome: Although focused on a single group, this evaluation lays the groundwork for understanding PPIE practices in LMIC contexts. It provides valuable insights into developing equitable partnerships and improving patient-centred research. This study contributes to a growing body of knowledge, offering practical guidance for implementing PPIE in settings with unique socioeconomic challenges and cultural realities. The findings are expected to benefit the local research community and similar initiatives globally, particularly in regions with comparable challenges.

Trypanosoma brucei is an extracellular eukaryotic parasite that causes sleeping sickness in humans and Nagana, Surra and Dourine in livestock, game animals and horses. The parasite displays an extensive immune evasion mechanism, utilising the expression and ability to switch antigenically distinct variant surface glycoprotein (VSG) coats. VSG encoding genes account for ~10% of the T. brucei genome, and mosaic VSGs, assembled from distinct incomplete VSG gene copies, can be produced from this VSG library, generating an almost infinite VSG repertoire, which enables chronic infections. Each parasite expresses just one VSG at a time, but within a host, many VSGs can be expressed simultaneously. Understanding patterns of VSG expression is therefore central to studying parasite dynamics, tissue tropism, and infection persistence. VSGSeq is an amplicon sequencing approach that enables surveillance of the population-wide diversity and abundance of expressed VSGs. We present vsgseq2, an updated and fully reproducible workflow for analysing VSGSeq data. Implemented in Nextflow, vsgseq2 integrates modern tools for transcript assembly and quantification, improves computational efficiency. Benchmarking against defined T. brucei VSG expression datasets demonstrated that vsgseq2 accurately reconstructs population-wide VSG repertoires and better recapitulates VSG expression proportions. Analyses of in vivo infection data further confirmed that vsgseq2 enhances reproducibility and improves data utilisation, and improves computational efficiency. vsgseq2 enables researchers to efficiently and reproducibly analyse complex VSG expression data and the mechanisms driving immune evasion in T. brucei.

Background: Learning platforms can strengthen primary healthcare (PHC) by integrating community knowledge with system decision-making, but evidence on how they work in low-resource settings is limited. This study presents a realist evaluation of the Verbal Autopsy with Participatory Action Research (VAPAR) learning platform in rural Mpumalanga, South Africa (2015-25). VAPAR aimed to embed participatory evidence generation and shared learning within routine district processes to support more equitable, community-linked PHC.

Methods: A realist design was used to synthesise data from five action-learning cycles (2017-23), a preceding pilot (2015-16), and an engagement and uptake phase (2023-25). Data included cycle reports, participatory outputs, verbal autopsy (VA) analyses, 22 endline interviews, policy, strategy and planning documents. Using a co-developed theory of change, qualitative data were coded to examine context-mechanism-outcome patterns. Mechanisms were identified and refined through cross-cycle comparison, triangulation, and stakeholder validation.

Results: VAPAR was contextually responsive, adapting to shocks such as COVID-19 and progressively embedding within the district health system. Through regular dialogue, the platform activated generative mechanisms of trust-building, role clarity and recognition, collective sense-making, and strengthened agency, particularly among Community Health Workers (CHWs), whose skills, confidence and legitimacy expanded. These mechanisms operated within an enabling structural context shaped by PHC reforms that strengthened the District Health System and Ward-Based Primary Health Care Outreach Teams, alongside trade-union action for CHW absorption into public service. Institutionalisation followed through Mpumalanga's revitalised Health Promotion Programme, with adaptation to additional provinces and for outbreak response and emergency obstetric care. Outcomes were interpreted through context-mechanism-outcome patterns, illustrating how participatory learning becomes embedded in decentralised health systems.

Conclusions: Over a decade, VAPAR demonstrated how structured, participatory learning can reshape relationships, strengthen community-linked PHC, and support institutionalisation of routine, evidence-informed practice in decentralised health systems. The findings offer transferable lessons for sustaining learning platforms in resource-constrained settings.

Background: Ayurveda, the traditional Indian medicine system, conceptualizes individual personality (Prakriti) through three dimensions, Vata, Pitta, and Kapha, based on physical, physiological, and psychological traits. Existing tools for Prakriti assessment often lack robust psychometric validation and accessibility. We developed and validated the Brief-Prakriti Inventory (BPI), a 21-item self-report instrument for assessing traditional Indian personality concepts.

Methods: An initial 30-item pool was derived from classical Ayurvedic texts and contemporary literature, covering three domains. Following pilot testing and psychometric screening, 21 items were retained. Items used nominal response formats, each mapped to a dosha, with randomized option order via REDCap. Psychometric evaluation employed Multiple Correspondence Analysis (MCA), Latent Class Analysis (LCA), and Item Response Theory (IRT) in a community sample (N = 1857). Validity was assessed via test-retest reliability, convergent validity with traditional AYUsoft assessments, and divergent validity using Western personality traits (Mini-IPIP).

Results: MCA revealed distinct dosha-aligned item clustering, particularly among participants with dominant dosha profiles ( Figure 1). LCA supported a three-class model (dominant-only: entropy R2 = 0.96) ( Figure 2, Supplementary Figure 1). IRT analyses showed strong fit (CFI = 0.967, RMSEA = 0.023) and good reliability (Vata = 0.87, Pitta = 0.75, Kapha = 0.87) ( Figure 3). Psychological items showed highest discrimination; physiological items displayed higher difficulty thresholds. Test-retest reliability was high (ICCs 0.83-0.90). BPI subscales correlated strongly with traditional assessments (r = 0.78-0.84) (Supplementary Figure 2) but minimally with Western personality traits ( Figure 4), supporting construct distinctiveness.

Conclusions: The BPI is a brief, reliable, psychometrically validated self-report tool that captures latent dosha typology consistent with Ayurvedic theory. By grouping individuals into Prakriti-based clusters, the BPI will enable biological phenotyping of dosha-linked variability and support personalized, culturally contextualized interventions in integrative and mental health care.

Background: Nutritional practices during early life are critical in shaping long-term health outcomes. Poor or inappropriate nutrition may influence adiposity gain and the overall cardiometabolic risk among children born with low birth weight. Our study investigates how early feeding patterns, the timing of adiposity rebound, and DNA methylation of key genes influence cardiometabolic health at two years in low-birth-weight children.

Methods: This study will be conducted as a longitudinal follow-up study among children with low birth weight (children born with a birth weight of less than 2500 grams). A thousand four hundred children will be recruited consecutively for this study. Birth weight, gestational age, and early neonatal and perinatal details will be collected from clinical records. Information on sociodemographic characteristics, dietary practices, and antenatal, obstetric, and postnatal histories will also be collected. The two-year follow-up assessment will include anthropometric measurements (height, weight, head circumference, chest circumference, waist circumference, and skinfold thickness) and blood pressure. Biochemical investigations will include a lipid profile, serum proteins, insulin resistance assessment, and hemoglobin levels. In addition, DNA methylation at six specific CpG sites relevant to adipogenesis and cardiometabolic health will be assessed. Left ventricular mass and ejection fraction will be evaluated using echocardiography. Carotid intima-media thickness will be measured using an appropriate ultrasound probe. The neurodevelopmental status of the children will be assessed using the Developmental Assessment Scales for Indian Infants (DASII) and Vineland Social Maturity Scale (VSMS).

Conclusions: Elucidating the impact of early life nutritional practices is vital for promoting cardiometabolic health. This understanding supports the formulation of tailored feeding interventions that are essential for safeguarding cardiovascular health in children with low birth weight.

Background: Respiratory syncytial virus (RSV) is a virus with two antigenic types, A and B, that cause significant morbidity and mortality in infants globally. A recently developed maternal vaccination based on the prefusion F protein ("RSVpreF") could have a significant impact on disease burden, if introduced globally. Whether or not the effectiveness of this vaccine is affected by circulating viral genomic variability is currently unknown.

Objectives: To examine whether the vaccine effectiveness of maternal RSVpreF administration in preventing hospitalisation in infants is affected by RSV type or lineage.

Methods: We will conduct whole genome sequencing of RSV positive samples from infants hospitalised with acute lower respiratory tract infection (ALRI) in the 2024-2025 winter season, at multiple hospitals in England and Scotland, to calculate the relative vaccine effectiveness (rVE) of maternal RSVpreF vaccination by virus type (RSV-A and RSV-B). rVE will be calculated using a case control logistic regression with adjustment by infant age and admission date; sex, socioeconomic status and hospital location will be included as potential confounders if they are associated with a >3% change in rVE. We will also perform a test negative design to examine the VE for RSV-A and RSV-B separately, using RSV-negative controls from hospitals where cases were admitted. Finally, we will compare viral lineages in vaccinated versus unvaccinated infants.

Results and conclusions: Our study will identify whether currently circulating RSV genomic variability impacts on rVE. Confirmation of the null hypothesis - that there is no impact of viral genomic variability on rVE - will provide reassurance to policymakers and public health bodies as RSVpreF is rolled out globally. Conversely, an association between RSV type or lineage and decreased vaccine effectiveness will highlight the need for the enhanced comprehensive national and global molecular surveillance of RSV.

Background: Neurological symptoms following head trauma are common; however, the cause may not always be obvious. In the absence of open wounds, fractures, or surgical interventions, infectious causes may not be considered, especially viral infections such as Herpes simplex, and investigations may not be targeted to investigate this possibility.

Case: A 39-year-old male presented with a severe headache, reduced consciousness, and confusion. Two days earlier, he had been discharged from the hospital, where he had been treated for traumatic brain injury with subarachnoid hemorrhage following a road traffic accident. Herpes simplex virus type 2 (HSV-2) was detected in the cerebrospinal fluid, confirming the diagnosis of viral meningoencephalitis. He was treated with oral aciclovir for two weeks and achieved full neurological recovery.

Conclusions: This case highlights the risk of viral reactivation following trauma, particularly head injuries. Central nervous system infections, including viral infections, should be considered in cases of delayed deterioration following trauma, likely presenting with worsening headache, drowsiness and reduced cognitive state. The optimal treatment of herpes simplex virus (HSV) encephalitis may be challenging in resource-limited settings.

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 reduced training, increasing accessibility. FlowCron transfers the responsibilities of installation and upkeep of data processing pipelines from users to HPC project PIs and/or HPC project managers, 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. For Globus to transfer any data to and from the HPC, appropriate user authentication is required, thus ensuring that only authorised users can send data in the HPC.

Background: Major histocompatibility class I (MHC-I, human leukocyte antigen [HLA] class I in humans) molecules present small fragments of the proteome on the cell surface for immunosurveillance, which is pivotal to control infected and malignant cells. Immunogenic peptides are generated and selected in the MHC-I antigen processing and presentation pathway. In this pathway, two homologous molecules, tapasin and TAPBPR, optimise the MHC-I peptide repertoire that is ultimately presented at the plasma membrane. Peptide exchange on HLA class I by human TAPBPR involves the flexible loop region K22-D35, with the leucine at position 30 (L30) involved in mediating peptide dissociation. However, our understanding of the exact molecular mechanisms governing TAPBPR-mediated peptide exchange on HLA class I allotypes remains incomplete.

Methods: Here, in-depth re-analyses of published immunopeptidomics datasets was used to further examine TAPBPR peptide editing activity and mechanism of action on HLA class I. The role of the TAPBPR editing loop in opening the HLA class I peptide binding groove was assessed using molecular dynamics simulations and a peptide exchange assay.

Results: We show that TAPBPR shapes the peptide repertoire on HLA-A, -B and -C allotypes. The TAPBPR editing loop was not essential to allow HLA class I to adopt an open state but did allow for the HLA-A*68:02 peptide binding groove to stay open for a sustained period. L30 in the TAPBPR editing loop was typically sufficient to mediate peptide repertoire restriction on the three HLA class I allotypes expressed by HeLa cells. TAPBPR was also able to load peptides onto HLA class I in a loop-dependent manner.

Conclusions: These results suggest that the TAPBPR editing loop is involved both in peptide filtering and loading.