NIHRDataInsights/HRCSData huggingface dataset:
Title: A04: Smoking behaviours and transitions to vaping in early adulthood: Investigating predictors with longitudinal data
Funder: Cancer Research UK

Abstract: Background Tobacco smoking remains a major global public health concern and is the leading cause of preventable cancer cases and deaths in the UK and globally. Currently, an estimated 1 billion people use tobacco products worldwide. Whilst cigarette use is declining in the United Kingdom (UK), it remains relatively common among young adults, with 16% of 18-24 year olds describing themselves as current smokers. Aims The over-arching aim of this project is to investigate predictors of smoking and vaping, in order to inform future cancer prevention strategies. This will be achieved through three specific objectives: 1. Investigating predictors of trajectories of smoking 2. Identifying predictors of the transition from smoking to vaping 3. Determining the role of parental smoking on offspring smoking and vaping behaviour Objectives 1 and 2 focus on identifying predictors of trajectories of smoking and vaping and potential intervention targets at the individual level. We will explore a broad range of potential predictors including other substance use, mental health, socioeconomic status, and sex. Familial influences are strong predictors of smoking and vaping (particularly in adolescence and young adulthood). Objective 3 will examine how parental smoking influences offspring smoking and vaping, and explore mechanisms through which this association acts. The additional data collection planned as part of this project will extend the longitudinal substance use information in the Avon Longitudinal Study of Parents and Children (ALSPAC) to approximately age 30 years and ensure that ALSPAC remains a rich source of data for future research into smoking behaviours. Methods We will use data from ALSPAC, a longitudinal population-based birth cohort. We will collect updated information on smoking and vaping on ALSPAC participants and use this to derive trajectories of smoking behaviours throughout adolescence and early adulthood using longitudinal latent class analysis. Logistic regression will be used to examine predictors of these trajectories. We will identify participants who have transitioned from smoking to vaping or abstinence and investigate predictors of this transition. Finally, we will look at the role of parental smoking on offspring smoking and vaping outcomes, including the role of mediating factors. How the results of this research will be used Understanding factors associated with smoking and vaping will inform future cancer prevention programmes and public health policy. This includes identifying predictors that can be used to tailor these programmes more effectively, as well as establishing potential intervention targets likely to have important downstream impacts on cancer prevalence.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: CANCER AND NEOPLASMS;CARDIOVASCULAR;RESPIRATORY;STROKE
Title: Action on Smoking and Health - full program of work 2022-25
Funder: Cancer Research UK

Abstract: Background This proposal is the latest in a series of applications for 3-year grants from CRUK to provide funding for ASH’s entire programme of work. This programme of work will take us to 2025 and within 5 years of the Government’s ambition for England to have adult smoking prevalence below 5% by 2030. This application is designed to secure the buy-in, commitment and delivery from across all tiers of government as well as civil society to reach this ambition. Aims The long-term aim is to make smoking obsolete and end the disparities in health outcomes caused by smoking. The key policy priorities are set out in the ASH-produced 2021 report for the All Party Parliamentary Group on Smoking and Health. CRUK, alongside other leading members of the Smokefree Action Coalition, have endorsed this report and its objectives overlap with the policy priorities set out by CRUK. Methods ASH’s strategy is underpinned by the scrupulous use of the evidence-base from research conducted by leading academics, as well as by CRUK and ASH with expert support. This proposal includes six strands in a planned programme of work which facilitates ASH’s three core functions: Campaigning: To press for particular concrete policy measures that will reduce the burden of addiction, disease, health inequalities and premature death attributable to tobacco. Information: To change the climate of understanding, opinion and awareness about the “tobacco epidemic” through effective use of the evidence base. Networking and coalition building: To engage and inform other organisations and persons in pursuing our information and campaigning work. Each of the seven workstreams in the proposed programme of work are set out below and have specific objectives and deliverables which are included in the full application: 1. The impact of current tobacco control policies optimised 2. Improvements in tobacco control policies secured 3. Address disparities in smoking rates 4. Tobacco industry interference in public health policy prevented 5. Agenda for tobacco control established/set with the media and professionals 6. Secure improvements in tobacco control policies internationally which support the UK 7. Synergistic working across risk factors optimised The proposed activities in this application should not be considered a prescriptive work programme, as to be most effective ASH must be able to react flexibly to changing political, economic and social circumstances as they arise. To this end the work programme is outcome-focused and flexible.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: CANCER AND NEOPLASMS;CARDIOVASCULAR;RESPIRATORY;STROKE
Title: Opportunity Led: Prof Frank Kee - Cessation of smoking in pregnancy (CPIT)
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: Those who smoke throughout life live on average 10 years less than non smokers or those who quit smoking by age 30 years. Those who give up permanently by age 40 years only lose 1 year of life. 80% of women have a baby, nearly all before age 40 years, so an effective intervention during pregnancy, that supports permanent cessation, will allow women to have a full lifespan. Previous trials of many interventions to help women stop smoking during pregnancy have not been very effective. Financial incentives have shown the most promise and in a recent pilot trial undertaken by our team may also be highly cost-effective depending on cessation being permanent. This trial aims to inform the National Institute for Health and Care Excellence (NICE) guideline PH26 Smoking: stopping in pregnancy and after childbirth to answer the first research question regarding financial incentives. This will allow the NICE guideline development group to recommend financial incentives (or not) as an addition to the current NHS pregnancy cessation service guidelines.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: CANCER AND NEOPLASMS;CARDIOVASCULAR;RESPIRATORY;STROKE;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Four-Year PhD Studentship in Basic Science UNS118254
Funder: Wellcome Trust

Abstract: Metabolic health depends on a myriad of genes and the environment. Variation in these genes across individuals can predispose them to obesity, Type II Diabetes (T2D) and other metabolic syndromes. Early works focused on how a few mutated genes could cause rare and severe metabolic diseases. A lot has been learnt about appetite and weight regulation by studying those genes whose mutations have large impact on metabolic health. However, common forms of obesity and T2D are attributed to multiple genetic variations, whose individual effects are hard to observe. We aim to understand how these mutations with little observable impacts affect our metabolic health. We hope to gain more insights into the fundamental genetics of metabolism from these rare mutations by combining data-driven epidemiological methods and molecular biology techniques. Epidemiological methods will statistically identify how the presence of some mutated genes correlate with alterations in metabolic health. Then, using molecular biology techniques, we will investigate the causations and mechanisms of these statistical correlations. To this end, we will clone the mutated genes in cellular models and measure the changes in their activities.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS;CARDIOVASCULAR;STROKE;METABOLIC AND ENDOCRINE;ORAL AND GASTROINTESTINAL
Title: Investigations into the role of EVI1 in Fanconi anaemia associated malignant transformation
Funder: Children with Cancer UK

Abstract: Fanconi anaemia (FA) is an inherited disease with extreme predisposition to leukaemia. FA results from a defect in a fundamental tumour suppressor pathway with a role in the DNA damage response. Haematopoietic cells in FA are characterised by hypersensitivity to DNA damaging agents, such as aldehydes, and a cell cycle arrest in the G2 phase. However, pre-leukaemic clonal cell populations with chromosomal aberrations in FA patients lose the FA-characteristic G2 arrest. As a key genetic event in leukaemogenesis associated with the FA defect we have identified activation of the EVI1 oncogene (Ecotropic Viral Integration Site 1). EVI1 is an oncogenic transcriptional regulator with an essential function in self-renewal and haematopoiesis. Deregulated EVI1 overexpression is oncogenic and alters cell cycle progression. In sporadic leukaemia EVI1 overexpression confers very poor prognosis on current treatment regimens. Our own investigations using EVI1 overexpressing FA-derived AML show absence of spontaneous G2 arrest, and indicate that EVI1 itself is modulated by DNA damage. We hypothesise that EVI1 activation confers a proliferative advantage in particular in the presence of an FA-defect and genotoxic stress, possible aldehydes. We want to explore the molecular and cellular mechanisms by which EVI1 confers a clonal proliferative advantage and malignant transformation in Fanconi anaemia, and study Evi1 in haematopoietic precursors in bone marrow cells from FA- and normal mice as a model of gene-environmentally driven leukaemogenesis.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS;CONGENITAL DISORDERS
Title: Edinburgh-St Andrews Consortium for Molecular Pathology, Informatics and Genome Sciences
Funder: Engineering and Physical Sciences Research Council

Abstract: The Edinburgh-St Andrews Molecular Pathology Node will integrate proven strengths in molecular pathology, (training, development and clinical implementation), image analysis of complex phenotypes, informatics and genomics to build expertise, quality assurance and capacity in 21st century molecular diagnostics. Drawing on additional strengths in the MRC Human Genetics Unit, MRC Farr Institute, CRUK Cancer Centre, EPSRC-funded supercomputer facilities and industrial collaborations, we will establish a Masters by Research in Molecular Pathology, and thus train a new generation of scientists who will develop new assays, algorithms and standards for genome and epigenome analysis and interpretation for clinical use. We will implement state-of-the-art genome technologies to mainstream molecular diagnosis of Mendelian diseases in adult medicine and establish rapid genetic diagnosis of acutely ill children and neonates. We will develop "liquid biopsies" for managing cancer via genetic and epigenetic analyses of tumours and cell-free circulating DNA and will use state-of-the art digital imaging, image analysis and spectroscopy of tumours to provide more precise diagnoses and predictive stratification for patient management. The leads for this proposal all work at the interface of academia and the NHS and, by defining diagnostic standards in collaboration with the UK National External Quality Assurance Scheme (UK NEQAS) for Molecular Pathology and Genetics, hosted in Edinburgh by NHS Lothian, can ensure that these innovations are translated rapidly to clinical practice in the NHS. The Node's activities will be dovetailed with industry at every stage: technology development, assay design and implementation, data interpretation and clinical validation. The new Molecular Pathology Masters programme will produce and sustain a generation of new academic pathologists and help create a virtual Centre for Molecular Pathology as a basis for a substantive MRC Centre in the longer term.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS;CONGENITAL DISORDERS
Title: Survey of cancer in Ataxia Telangiectasia patients in the UK
Funder: Action for A-T

Abstract: This project will survey the known cases of cancer in Ataxia Telangiectasia patients in the UK

Lay abstract: Building on their initial pilot study in 2011, Professor Taylor and his team at the Institute of Cancer and Genomic Sciences will perform a detailed survey of cancer incidence in a cohort of ~300 UK individuals with A-T to gain a more accurate assessment of the tumour types that individuals develop. The cohort of patients are registered with the national A-T clinic in Nottingham where Professor Taylor is well known having diagnosed the ATM mutations in virtually all 300 patients. Approximately 200 are still alive, some having already been treated for a cancer and of the ~100 that are deceased, 50% were due to cancer. The data on cancers in this population will be analysed in a standard manner, in terms of the types of tumour and incidence rates of the different cancers compared to the normal population. Where tumour material is available, further molecular characterisation of the tumours using techniques such as whole genome sequencing and RNA-Seq will be performed. These will give a detailed assessment of both the mutational and transcriptional spectrum of the tumours and provide insight into the cancer phenotype within A-T, identifying the genetic drivers and biochemical pathways that promote and maintain this phenotype.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS;CONGENITAL DISORDERS
Title: Molecular mechanisms of eukaryotic ribosome biogenesis
Funder: Medical Research Council

Abstract: Ribosome assembly is an essential, highly conserved process that is tightly coupled to cell growth and proliferation. However, the molecular mechanism underlying this process remains poorly understood. Excitingly, a new class of cancer predisposition syndromes collectively called the "ribosomopathies" has recently emerged that harbour mutations in components of the ribosome assembly pathway that are shedding new light on this process. In particular, we have discovered that the SBDS protein that is deficient in the leukaemia predisposition disorder Shwachman-Diamond syndrome is required for maturation of the large ribosomal subunit. SBDS controls the translational activation of ribosomes by catalysing dissociation of the anti-association factor eIF6 from nascent 60S subunits, but the precise mechanism remains unclear. We propose a model in which GTP-dependent conformational change in elongation factor-like 1 (EFL1) induces an inter-domain rotation in SBDS that directly or indirectly triggers eIF6 release. We aim to test this hypothesis at the molecular level by combining the latest advances in single-particle cryo-electron microscopy and NMR spectroscopy with X-ray crystallography, biochemistry and innovative genetic platforms. We will test the hypothesis that eIF6 release is a prerequisite for eviction of additional assembly factors whose specific role in ribosome assembly we will determine. Novel insights into the mechanisms of ribosome assembly are not only exploitable for the design of targeted therapeutics for the ribosomopathies, but also for cancer drug discovery more generally.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: CANCER AND NEOPLASMS;CONGENITAL DISORDERS;GENERIC HEALTH RELEVANCE
Title: Muslim family screening for life
Funder: Yorkshire Cancer Research

Abstract: Bradford Muslim South Asian women are less likely to have cervical, breast and bowel screening than other women increasing their risks of dying from cancer. These women often rely on men to have their screening, but the support needed can be lacking. Research is urgently needed to develop ways that men can actively help women have screening. We will work in partnership with experienced community groups, Muslim men and women including Leaders and Imams to sensitively co-design, develop and test an intervention for Muslim men aged 16+. The intervention will be delivered in Mosques, Madrassas, educational settings, youth groups and peer support groups to 1000 men in five Bradford postcodes. Men will also receive motivational text messages and access a website to encourage them to support female family members to have overdue screening. We will collect data to see how well the intervention worked. Methods will include surveys, interviews and recording the sessions being delivered. We will collect GP data, looking for increased screening in these postcodes compared to other areas. We will learn about the importance of including men in promoting women’s screening and estimate 1550 overdue cancer screens in women will take place as a result.

Lay abstract: Bradford Muslim South Asian women are less likely to have cervical, breast and bowel screening than other women increasing their risks of dying from cancer. These women often rely on men to have their screening, but the support needed can be lacking. Research is urgently needed to develop ways that men can actively help women have screening. We will work in partnership with experienced community groups, Muslim men and women including Leaders and Imams to sensitively co-design, develop and test an intervention for Muslim men aged 16+. The intervention will be delivered in Mosques, Madrassas, educational settings, youth groups and peer support groups to 1000 men in five Bradford postcodes. Men will also receive motivational text messages and access a website to encourage them to support female family members to have overdue screening. We will collect data to see how well the intervention worked. Methods will include surveys, interviews and recording the sessions being delivered. We will collect GP data, looking for increased screening in these postcodes compared to other areas. We will learn about the importance of including men in promoting women’s screening and estimate 1550 overdue cancer screens in women will take place as a result.

Research activity codes: 4.3 INFLUENCES AND IMPACT
Health categories: CANCER AND NEOPLASMS;DISPUTED AETIOLOGY AND OTHER
Title: Developing an evidence-based psycho-educational intervention for teenagers and young adults who have had retinoblastoma
Funder: Childhood Eye Cancer Trust

Abstract: There is little guiding evidence about the specific challenges that teenagers who have had retinoblastoma face as they transition towards young adulthood. Understanding the psycho-educational needs of teenagers and young adults as they transition into adulthood is therefore essential if we are to offer effective interventions to support them. This PhD studentship aims to develop an evidence-based intervention for teenagers and young adults with retinoblastoma that offers relevant, accessible and effective psycho-educational support.

Lay abstract: There is little guiding evidence about the specific challenges that teenagers who have had retinoblastoma face as they transition towards young adulthood. Understanding the psycho-educational needs of teenagers and young adults as they transition into adulthood is therefore essential if we are to offer effective interventions to support them. This PhD studentship aims to develop an evidence-based intervention for teenagers and young adults with retinoblastoma that offers relevant, accessible and effective psycho-educational support.

Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: CANCER AND NEOPLASMS;EYE
Title: Direct labelling of proteins using Affimer-conjugate warheads for imaging
Funder: Biotechnology and Biological Sciences Research Council

Abstract: Recently there has been an increase in the use of alternatives to antibodies in super-resolution microscopy, including nanobodies, Affibodies, and Affimers. These reagents are approximately 10 times smaller than antibodies, and bind with similar levels of specificity and affinity. Anti-GFP nanobody, used to target GFP-fusion proteins, reduced the linkage error to ~2nm. The anti-HER-2 Affibody has also shown promise in super-resolution microscopy, enabling visualisation of the intra- and intercellular distribution patterns of HER-2 in over-expressing cancer cells. Affimers, developed by DT, have been used in a range of assays from diagnostics to blocking protein-protein interactions. In super-resolution microscopy Affimers have been used to image tubulin and HER4, as well as other unpublished targets including actin and actinin. Although binding reagents like Affimers provide improve resolution by placing the fluorophore in close proximity to the protein, as super-resolution microscopy techniques and technologies improve the resolution will increase, making even small binding reagents a limiting factor. Potential methods of overcoming this issue are to use over-expressed tagged target proteins fused or genetically modified for direct incorporation of fluorophores in non-natural amino acids. Although useful these methods still require over-expression or genetic modification of target and cell to enable visualisation. A more appealing approach would be to generate a technique capable of directly labelling endogenous proteins therefore reducing the chances of altering protein function by overexpression or tagging. Hence, the aim is to develop methods to directly label endogenous proteins with fluorophores by targeting them with Affimers functionalised with a reactive fluorophore warhead.


Research activity codes: 1.3 CHEMICAL AND PHYSICAL SCIENCES
Health categories: CANCER AND NEOPLASMS;GENERIC HEALTH RELEVANCE