NIHR Liverpool Pancreatic Biomedical Research Unit

Abstract BackgroundThe ability to manage finances is one of the first daily activities to deteriorate in dementia. With finance tasks having gone even more remotely and digitalised since the pandemic, the aim of this qualitative interview study was to explore how finance management and spending habits of people with dementia living in the community may have been affected by the pandemic.MethodWe remotely interviewed 30 unpaid carers and people with dementia across the UK from February to May 2022 about their experiences of managing finances and spending habit changes during the pandemic. The topic guide was co‐developed with two unpaid carers. Data were analysed using inductive thematic analysis.ResultThe pandemic fast‐tracked the digitalisation of finance management tasks for people with dementia, which caused inequalities for many who were unfamiliar with digital formats. This necessitated further involvement of unpaid family carers in all aspects of finance management on behalf of the person living with dementia, leading to increased caring duties on top of existing tasks. Navigating the legalities surrounding financing care for dementia was similarly found to be characterised by barriers for most, with those from more socio‐economically disadvantaged backgrounds receiving less help to source financial support.ConclusionSupport needs to be in place for people with dementia to manage their finances digitally, whilst carers need to be provided with clear guidance and support in how to navigate this daily activity. Legal arrangements with banks and other organisations should be in place as soon as possible to enable equitable support with this key daily activity.

Long COVID (LC) affects approximately 45% of COVID-19 survivors, 1 featuring persistent symptoms lasting over 4 weeks without an alternative explanation. 2 The recent development of LC services aims to provide structured or integrated care. 3 Given the current challenges in the UK healthcare system, we explored access to care for people with LC. We compared this to other long-term conditions (LTCs), concerning four filters for accessing care as defined in the Pathways-to-Care model, 4 to inform policy and service planning across diseases and specialities. Those filters include the person's decision to seek care (filter 1), the decision of the General Practitioner (GP) to provide diagnosis and treatment in primary care (filter 2), the GP's decision to refer the patient to specialist care (filter 3), and the arrival of the patient in outpatient specialist care (filter 4). The second filter concerns a complex process combining the patient's perspective of their health problems being recognized by the GP and diagnostic, treatment, or referral actions taken by GPs that indicate that the GP recognized the patient's problem. We expanded this recognition concept to include other healthcare professionals (HCPs) in primary care. We conducted an online survey from April to June 2022 as part of the STIMULATE-ICP-Delphi study. Using snowball sampling, we recruited 283 participants, including patients and HCPs, with experience in LC and LTCs. We incorporated patient and public involvement and used descriptive statistics. The protocol for this Delphi study was

Background. Human embryonic stem cells (hESCs) are pluripotent cells derived from the inner cell mass of in vitro fertilised blastocysts, which can either be maintained in an undifferentiated state or committed into lineages under determined culture conditions. These cells offer great potential for regenerative medicine, but at present, little is known about the mechanisms that regulate hESC stemness; in particular, the role of cell-cell and cell-extracellular matrix interactions remain relatively unexplored. Methods and results. In this study we have performed an in silico analysis of cell-microenvironment interactions to identify novel proteins that may be responsible for the maintenance of hESC stemness. A hESC transcriptome of 8,934 mRNAs was assembled using a meta-analysis approach combining the analysis of microarrays and the use of databases for annotation. The STRING database was utilised to construct a protein-protein interaction network focused on extracellular and transcription factor components contained within the assembled transcriptome. This interactome was structurally studied and filtered to identify a short list of 92 candidate proteins, which may regulate hESC stemness. Conclusion. We hypothesise that this list of proteins, either connecting extracellular components with transcriptional networks, or with hub or bottleneck properties, may contain proteins likely to be involved in determining stemness.

Background. Human embryonic stem cells (hESCs) are pluripotent cells derived from the inner cell mass of in vitro fertilised blastocysts, which can either be maintained in an undifferentiated state or committed into lineages under determined culture conditions. These cells offer great potential for regenerative medicine, but at present, little is known about the mechanisms that regulate hESC stemness; in particular, the role of cell-cell and cell-extracellular matrix interactions remain relatively unexplored. Methods and results. In this study we have performed an in silico analysis of cell-microenvironment interactions to identify novel proteins that may be responsible for the maintenance of hESC stemness. A hESC transcriptome of 8,934 mRNAs was assembled using a meta-analysis approach combining the analysis of microarrays and the use of databases for annotation. The STRING database was utilised to construct a protein-protein interaction network focused on extracellular and transcription factor components contained within the assembled transcriptome. This interactome was structurally studied and filtered to identify a short list of 92 candidate proteins, which may regulate hESC stemness. Conclusion. We hypothesise that this list of proteins, either connecting extracellular components with transcriptional networks, or with hub or bottleneck properties, may contain proteins likely to be involved in determining stemness.

Cell communication is central to the integration of cell function required for the development and homeostasis of multicellular animals.Proteins are an important currency of cell communication, acting locally (auto-, juxta-, or paracrine) or systemically (endocrine).The fibroblast growth factor (FGF) family contributes to the regulation of virtually all aspects of development and organogenesis, and after birth to tissue maintenance, as well as particular aspects of organism physiology.In the West, oncology has been the focus of translation of FGF research, whereas in China and to an extent Japan a major focus has been to use FGFs in repair and regeneration settings.These differences have their roots in research history and aims.The Chinese drive into biotechnology and the delivery of engineered clinical grade FGFs by a major Chinese research group were important enablers in this respect.The Chinese language clinical literature is not widely accessible.To put this into context, we provide the essential molecular and functional background to the FGF communication system covering FGF ligands, the heparan sulfate and Klotho co-receptors and FGF receptor (FGFR) tyrosine kinases.We then summarise a selection of clinical reports that demonstrate the efficacy of engineered recombinant FGF ligands in treating a wide range of conditions that require tissue repair / regeneration.Alongside, the functional reasons why application of exogenous FGF ligands does not lead to cancers are described.Together, this highlights that the FGF ligands represent a major opportunity for clinical translation that has been largely overlooked in the West.

Objectives:Pancreatic intraductal papillary mucinous neoplasias (IPMNs) represent 25% of all cystic neoplasms and are precursor lesions for pancreatic ductal adenocarcinoma. This study aims to identify the best imaging modality for detecting malignant transformation in IPMN, the sensitivity and specificity of risk features on imaging, and the usefulness of tumor markers in serum and cyst fluid to predict malignancy in IPMN.Methods:Databases were searched from November 2006 to March 2014. Pooled sensitivity and specificity of diagnostic techniques/imaging features of suspected malignancy in IPMN using a hierarchical summary receiver operator characteristic (HSROC) approach were performed.Results:A total of 467 eligible studies were identified, of which 51 studies met the inclusion criteria and 37 of these were incorporated into meta-analyses. The pooled sensitivity and specificity for risk features predictive of malignancy on computed tomography/magnetic resonance imaging were 0.809 and 0.762 respectively, and on positron emission tomography were 0.968 and 0.911. Mural nodule, cyst size, and main pancreatic duct dilation found on imaging had pooled sensitivity for prediction of malignancy of 0.690, 0.682, and 0.614, respectively, and specificity of 0.798, 0.574, and 0.687. Raised serum carbohydrate antigen 19-9 (CA19-9) levels yielded sensitivity of 0.380 and specificity of 0903. Combining parameters yielded a sensitivity of 0.743 and specificity of 0.906.Conclusions:PET holds the most promise in identifying malignant transformation within an IPMN. Combining parameters increases sensitivity and specificity; the presence of mural nodule on imaging was the most sensitive whereas raised serum CA19-9 (>37 KU/l) was the most specific feature predictive of malignancy in IPMNs.

Cell communication is central to the integration of cell function required for the development and homeostasis of multicellular animals. Proteins are an important currency of cell communication, acting locally (auto-, juxta-, or paracrine) or systemically (endocrine). The fibroblast growth factor (FGF) family contributes to the regulation of virtually all aspects of development and organogenesis, and after birth to tissue maintenance, as well as particular aspects of organism physiology. In the West oncology has been the focus of translation of FGF research, whereas in China and to an extent Japan a major focus has been to use FGFs in repair and regeneration settings. These differences have their roots in research history and aims. The Chinese drive into biotechnology and the delivery of engineered clinical grade FGFs by a major Chinese research group were important enablers in this respect. The Chinese language clinical literature is not widely accessible. To put this into context, we provide the essential molecular and functional background to the FGF communication system covering FGF ligands, the heparan sulfate and Klotho co-receptors and FGF receptor (FGFR) tyrosine kinases. We then summarise a selection of case reports that demonstrate the efficacy of engineered recombinant FGF ligands in treating a wide range of conditions that require tissue repair / regeneration. Alongside the functional reasons why application of exogenous FGF ligands does not lead to cancers are described. Together, this highlights that the FGF ligands represent a major opportunity for clinical translation, that has been largely overlooked in the West.