Abstract Background Aβ42/Aβ40 ratios in cerebrospinal fluid (CSF) and blood are reduced in preclinical Alzheimer’s disease (AD), but their temporal and correlative relationship with cerebral Aβ pathology at this early disease stage is not well understood. In the present study, we aim to investigate such relationships using App knock-in mouse models of preclinical AD. Methods CSF, serum, and brain tissue were collected from 3- to 18-month-old AppNL−F/NL−F knock-in mice (n = 48) and 2–18-month-old AppNL/NL...

Abstract Background Both post-COVID-19 condition (long COVID) and the presence of persisting symptoms that do not meet formal definitions of post-COVID-19-condition may adversely affect quality of life and function. However, their prevalence among children and young people in England is unclear. Methods We used data from repeated surveys in a large cohort of English schoolchildren from the COVID-19 Schools Infection Survey (SIS) for the school year 2021/22 to describe the weighted prevalence of post-COVID-19-condition and...

Abstract Background Postoperative hypotension is common after major non-cardiac surgery, due predominantly to vasodilation. Administration of infused vasopressors postoperatively may often be considered a surrogate indicator of vasodilation. The incidence of postoperative vasopressors has never been described for non-cardiac surgery, nor have outcomes associated with their use. This paper presents a protocol for a prospective international cohort study to address these gaps in knowledge. The primary objectives are to estimate the proportion of patients who...

Abstract Background Influenza is a major year-round cause of respiratory illness in Kenya, particularly in children under 5. Current influenza vaccines result in short-term, strain-specific immunity and were found in a previous study not to be cost-effective in Kenya. However, next-generation vaccines are in development that may have a greater impact and cost-effectiveness profile. Methods We expanded a model previously used to evaluate the cost-effectiveness of seasonal influenza vaccines in Kenya to include next-generation vaccines...

Abstract Background Influenza is a major year-round cause of respiratory illness in Kenya, particularly in children under 5. Current influenza vaccines result in short-term, strain-specific immunity and were found in a previous study not to be cost-effective in Kenya. However, next-generation vaccines are in development that may have a greater impact and cost-effectiveness profile. Methods We expanded a model previously used to evaluate the cost-effectiveness of seasonal influenza vaccines in Kenya to include next-generation vaccines...

Abstract Background Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystem illness characterized by substantial reduction in function accompanied by profound unexplained fatigue not significantly relieved by rest, post-exertional malaise, and other symptoms. Reduced natural killer (NK) cell count and cytotoxicity has been investigated as a biomarker for ME/CFS, but few clinical laboratories offer the test and multi-site verification studies have not been conducted. Methods We determined NK cell counts and cytotoxicity in 174 (65%) ME/CFS,...

Abstract Background RNA-sequencing (RNA-seq) has been widely used to study the dynamic expression patterns of transcribed genes, which can lead to new biological insights. However, processing and analyzing these huge amounts of histological data remains a great challenge for wet labs and field researchers who lack bioinformatics experience and computational resources. Results We present BarleyExpDB, an easy-to-operate, free, and web-accessible database that integrates transcriptional profiles of barley at different growth and developmental stages, tissues, and...

Abstract Background RNA-sequencing (RNA-seq) has been widely used to study the dynamic expression patterns of transcribed genes, which can lead to new biological insights. However, processing and analyzing these huge amounts of histological data remains a great challenge for wet labs and field researchers who lack bioinformatics experience and computational resources. Results We present BarleyExpDB, an easy-to-operate, free, and web-accessible database that integrates transcriptional profiles of barley at different growth and developmental stages, tissues, and...

Abstract Background Depression is one of the most common mental health problems worldwide and, while prevalence rates in Latin America are relatively high, most people who meet the criteria for diagnosis do not receive treatment. Family and friends of a person with depression can play an important role in supporting a person to seek and engage with treatment. However, many people do not have the necessary skills or confidence to help. English-language mental health first...

Abstract Background Alzheimer’s disease (AD) is the 5th leading cause of death in people 65 years and older. The ATN classification reflects a biological definition of AD pathology with markers of Aβ deposition (A), pathologic tau (T), and neurodegeneration (N). Little is known about the relationship between ATN status and the risk of mortality, leading us to examine this association in a relatively large population of patients seen at a memory clinic for cognitive disorders....

Abstract Background Alzheimer’s disease (AD) is a complex and heterogeneous disease, which requires reliable biomarkers for diagnosis and monitoring disease activity. Preanalytical protocol and technical variability associated with biomarker immunoassays makes comparability of biomarker data across multiple cohorts difficult. This study aimed to compare cerebrospinal fluid (CSF) biomarker results across independent cohorts, including participants spanning the AD continuum. Methods Measured on the NeuroToolKit (NTK) prototype panel of immunoassays, 12 CSF biomarkers were evaluated from three...

Abstract Background Plasma neurofilament light (NfL) is an indicator of neurodegeneration and/or neuroaxonal injury in persons with Alzheimer’s disease (AD) and a wide range of other neurological disorders. Here, we characterized and compared plasma NfL concentrations in cognitively unimpaired (CU) late-middle-aged and older adults with two, one, or no copies of the APOE ε4 allele, the major genetic risk factor for AD. We then assessed plasma NfL associations with brain imaging measurements of AD-related neurodegeneration...

Abstract Background The CRADLE (Community blood pressure monitoring in Rural Africa: Detection of underLying pre-Eclampsia) Vital Signs Alert device—designed specifically to improve maternity care in low resource settings—had varying impact when trialled in different countries. To better understand the contextual factors that may contribute to this variation, this study retrospectively evaluated the adoption of CRADLE, during scale-up in Sierra Leone. Methods This was a mixed methods study. A quantitative indicator of adoption (the proportion of...

Abstract Background For children and young people with eye and vision conditions, research is essential to advancing evidence-based recommendations in diagnosis, prevention, treatments and cures. Patient ‘experience’ reflects a key measure of quality in health care (Department of Health. High Quality Care for All: NHS Next Stage Review Final Report: The Stationery Office (2008)); research participant ‘experiences’ are equally important. Therefore, in order to achieve child-centred, high-quality paediatric ophthalmic research, we need to understand participation...

Abstract Background Progressive familial intrahepatic cholestasis type 3 (PFIC3) is an autosomal recessive disease caused by pathogenic variants of the gene ABCB4. This study aimed to investigate the ABCB4 genotypic and the clinical phenotypic features of PFIC3 patients. Methods The clinical and molecular genetic data of 13 new pediatric patients with PFIC3 as well as 82 reported ones in the PubMed and CNKI databases were collected and analyzed. Results The 13 new PFIC3 patients included...

Abstract Background Increased neurofilament levels in biofluids are commonly used as a proxy for neurodegeneration in several neurodegenerative disorders. In this study, we aimed to investigate the distribution of neurofilaments in the cerebral cortex of Parkinson’s disease (PD), PD with dementia (PDD) and dementia with Lewy bodies (DLB) donors, and its association with pathology load and MRI measures of atrophy and diffusivity. Methods Using a within-subject post-mortem MRI-pathology approach, we included 9 PD, 12 PDD/DLB...

Abstract Background Dementia leads to multiple issues including difficulty in communication and increased need for care and support. Discussions about the future often happen late or never, partly due to reluctance or fear. In a sample of people living with dementia and carers, we explored their views and perceptions of living with the condition and their future. Methods Semi-structured interviews were conducted in 2018-19 with 11 people living with dementia and six family members in...

Abstract Background Preclinical studies have demonstrated the potential use of induced pluripotent stem cells (iPSCs) to treat cardiovascular disease (CVD). In vivo preclinical studies conducted on animal models (murine, porcine, guinea pig, etc.) have employed either syngeneic or human-derived iPSCs. However, no study has been carried out to investigate and report the key genetic differences between the human and animal-derived iPSCs. Our study analysed the gene expression profile and molecular pathway patterns underlying the differentiation...

Abstract Background There is a lack of studies focusing on the benefit of liver transplantation (LT) in hepatocellular carcinoma (HCC) patients with > 3 tumors. This study aims to establish a model to effectively predict overall survival in Chinese HCC patients with multiple tumors (> 3 tumors) who undergo LT. Methods This retrospective study included 434 HCC liver transplant recipients from the China Liver Transplant Registry. All HCC patients had more than 3 tumor nodules....

Abstract Background Cross-sectional studies suggest a relationship between diabetes status and weaker grip strength (GS) in adulthood and limited evidence from longitudinal studies has focussed on the association with average change in GS. We aimed to investigate whether diabetes status was related to membership of distinct GS trajectories in mid-to-late adulthood in 2,263 participants in the Medical Research Council National Survey of Health and Development. Methods Grip strength (kg) was measured at 53, 60–64 and...

Abstract Background Depression is one of the most common mental health problems worldwide and, while prevalence rates in Latin America are relatively high, most people who meet the criteria for diagnosis do not receive treatment. Family and friends of a person with depression can play an important role in supporting a person to seek and engage with treatment. However, many people do not have the necessary skills or confidence to help. English-language mental health first...

Abstract Human middle temporal gyrus (MTG) is a vulnerable brain region in early Alzheimer’s disease (AD), but little is known about the molecular mechanisms underlying this regional vulnerability. Here we utilize the 10 × Visium platform to define the spatial transcriptomic profile in both AD and control (CT) MTG. We identify unique marker genes for cortical layers and the white matter, and layer-specific differentially expressed genes (DEGs) in human AD compared to CT. Deconvolution of...

Abstract Background Introducing a de-novo home haemodialysis (HHD) program often raises safety concerns as errors could potentially lead to serious adverse events. Despite the complexity of performing haemodialysis at home without the supervision of healthcare staff, HHD has a good safety record. We aim to pre-emptively identify and reduce the risks to our new HHD program by risk assessment and using failure mode and effects analysis (FMEA) to identify potential defects in the design and...

Abstract Background Youth alcohol consumption has fallen markedly over the last twenty years in England. This paper explores the drivers of the decline from the perspectives of young people. Methods The study used two methods in a convergent triangulation design. We undertook 38 individual or group qualitative interviews with 96 participants in various educational contexts in England. An online survey of 547 young people in England, was also conducted. Participants were aged between 12–19 years....

Abstract Background Global connectivity and environmental change pose continuous threats to dengue invasions from worldwide to China. However, the intrinsic relationship on introduction and outbreak risks of dengue driven by the landscape features are still unknown. This study aimed to map the patterns on source-sink relation of dengue cases and assess the driving forces for dengue invasions in China. Methods We identified the local and imported cases (2006–2020) and assembled the datasets on environmental conditions....