NIHRDataInsights/HRCSData huggingface dataset:
Award Title: PHASE: The Population Health Agent based Simulation nEtwork
Funder: Medical Research Council

Abstract: Major population health challenges including non-communicable diseases are not a product of simple, linear causal relationships, but of numerous interdependent and interacting processes, operating at multiple levels.  In this context, population health research is increasingly adopting the complex systems perspective - a whole-system view centered on modelling the interactions between individuals and their social and physical environments. Agent-based modelling (ABM) is a complex systems simulation methodology that models individuals embedded in a physical and social environment, with their actions determined by simple decision rules.  ABMs can model both individual health behaviours and their upstream determinants, enabling us to better understand the tangled web of processes that drive health and generate inequalities at the population level. PHASE will facilitate the application of ABMs in population health through education, training and collaboration.  Network activities will address issues of critical importance to enabling population health researchers and decision makers to apply ABMs: appropriate problem domains; best practices for model development; technical training; and ABM reporting guidelines. Working groups will develop documentation protocols, best-practice guidelines, and computational training. Our initial membership includes population health scientists, ABM specialists, health policy and practitioner groups and industrial collaborators, all of whom will be invited to contribute to our events and working groups. PHASE will also create an ABM study registry that will allow stakeholders to seek help with problems that may benefit from an ABM approach.  PHASE will particularly seek to engage with evidence users and researchers from multiple disciplines to generate new transdisciplinary teams that will apply ABMs to important challenges in the prevention of non-communicable disease. This grant is funded by the UK Prevention Research Partnership (UKPRP) which is administered by the Medical Research Council on behalf of the UKPRP's 12 funding partners: British Heart Foundation; Cancer Research UK; Chief Scientist Office of the Scottish Government Health and Social Care Directorates; Engineering and Physical Sciences Research Council; Economic and Social Research Council; Health and Social Care Research and Development Division, Welsh Government; Health and Social Care Public Health Agency, Northern Ireland; Medical Research Council; Natural Environment Research Council; National Institute for Health Research; The Health Foundation; The Wellcome Trust.


Research Activity Codes: 2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY);2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);3.5 RESOURCES AND INFRASTRUCTURE (PREVENTION)
Health Categories: GENERIC HEALTH RELEVANCE
Award Title: POSE-D – Providing Online Self help for Eating disorders in Diabetes
Funder: Diabetes UK

Abstract: Background: Binge eating disorder (BED) has been identified as a significant problem in people with Type 2 diabetes. There are currently no psychological interventions for BED tailored to the needs of this group that can be delivered within diabetes services.
Aim: To develop an acceptable and effective treatment for BED in people with Type 2 diabetes
Methods: An 18 month project with two Work streams. In Work stream 1 - we will adapt an existing, online brief psychological intervention for BED called Guided self-help, for adults with Type 2 diabetes. The intervention has been developed by the research team and is evidence-based. We will conduct four co-design workshops with patients and healthcare professionals separately. In Work stream 2 we will test the feasibility of recruitment, research processes and delivery of the intervention in a case series with 10 participants. We will conduct qualitative interviews with participants to access acceptability.
Impact: A brief tailored psychological intervention to help people with Type 2 diabetes to reduce binge eating and the parameters necessary to conduct a full trial.

PPI: We will involve our Service User Involvement Facilitator and PPI Advisory Group throughout the research to inform the grant, patient materials and dissemination.


Research Activity Codes: 7.1 INDIVIDUAL CARE NEEDS;6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health Categories: METABOLIC AND ENDOCRINE;MENTAL HEALTH
Award Title: PRECISION VISION - Using AI for Early Detection and Diagnosis of Head and Neck Pre-cancer and Cancer
Funder: Cancer Research UK

Abstract: BACKGROUND
Head and neck cancers (HNC) are amongst the top ten most common cancers in the world with increasing frequency, poor prognosis and no improvement in survival due to late detection. Patients require extensive surgery and/or chemo/radiotherapy with significant morbidity, poor quality of life and no improvement in survival. Hence, there is a dire need for early identification and referral of these lesions to specialist centres for early intervention. The majority of HNC are preceded by a pre-cancerous stage but a biopsy is required for diagnosis. Photographs of such head and neck (H&N) lesions are taken in tertiary care as a standard-of-care. Some clinical features such as shape and colour etc. can be suggestive of pre-malignancy/malignancy, however, analysis is subjective with inter-observer variability and these features may not be evident sometimes, leading to missed or late diagnoses. There have been significant developments in Artificial Intelligence (AI) for diagnosis and treatment in the last few years. However, its use in clinical diagnosis of H&N cancers has not been reported to date.
AIMS
To use AI for analysis of clinical images of H&N lesions for early and objective detection of cancer or dysplasia. 
METHODS
Digital images of lesions will be used to optimise/develop and test AI algorithms. Retrospective lesion images with a confirmed histopathological diagnosis will be used for annotations during training and validation. Subsequently the algorithm will be tested on an unseen cohort to determine accuracy, sensitivity and specificity. Correlation with demographics, smoking/alcohol history and prognosis will also be performed. 
HOW THE RESULTS OF THIS RESEARCH WILL BE USED
The main intended outcome is to aid patient triaging and early referral, diagnosis and treatment even before the biopsy stage. It will facilitate establishment of the proposed collaboration, a relevant dataset and pave the way for future grant applications. Data will be presented at conferences to engage patients, clinical/academic colleagues and published in high quality journals and the dataset shaed with other investigators.


Research Activity Codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health Categories: CANCER AND NEOPLASMS
Award Title: PROTEOME-WIDE IDENTIFICATION OF RNA-BINDING PROTEINS PLAYING CRITICAL ROLES IN VIRUS INFECTION
Funder: Medical Research Council

Abstract: RNA viruses rely extensively on host RNA-binding proteins (RBPs) to accomplish their biological cycle, offering new possibilities of antiviral intervention. However, the repertoire of RBPs involved in virus infection has remained largely uncharacterised. To uncover the scope of RBPs that interact with viral RNAs in infected cells, we will develop a new method, referred to here as viral (v) RNP capture, using Sindbis virus (SINV) as discovery model. In brief, viral RNAs will be labelled with the nucleotide analogue 4-thiouridine (4SU) in presence of actinomycin D, which inhibits host RNA polymerases, directing 4SU incorporation exclusively to viral RNAs. After labelling, crosslinking between RBPs and viral RNAs will be achieved by irradiation with 365nm ultraviolet light. Proteins covalently linked to viral RNAs will be purified following stringent purification via oligo (dT) and identified quantitative proteomics. Resulting datasets will be used to select candidates for functional assays. Applying an in-house developed mid-throughput approach, we plan to study the effects of RBP overexpression, knock out and inhibition not only in cells infected with SINV but also with closely related and unrelated human pathogens. Finally, the role of RBPs exhibiting strong phenotypes in infection will be studied from a mechanistic perspective combining state-of-the-art methods in virology, RNA biology, super-resolution microscopy and proteomics. We expect to identify fundamental RBPs with regulatory roles in infection that can become antiviral targets for host-based therapies.


Research Activity Codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health Categories: INFECTION
Award Title: Pain Centre Versus Arthritis
Funder: Versus Arthritis

Abstract: The integration of preclinical and clinical expertise within the Arthritis Research UK Pain Centre, coupled with external collaborations, has led to fundamental advances in our understanding of OA pain mechanisms.  Key achievements during our first 5 years include identifying discrete pain mechanisms that map to OA pain phenotype both in patients and in animal models, and the integration of preclinical and clinical studies to demonstrate the mechanisms by which NGF, osteoclasts, TRPV1, and CGRP in the joint, spinal sensitization, psychological distress and augmented central pain processing each contribute to OA pain. This new knowledge has informed a multimodal model of knee OA pain, which integrates joint pathology, alterations in peripheral and central pain processing, changing brain morphology and function and psychological factors. During the next 5 years, we will capitalise on these achievements to
test mechanistically targeted and novel treatment strategies which reduce the burden of pain in people living with arthritis
identify mechanisms of pain progression which can be targeted to substantially reduce the future burden of arthritis.

An integrated, multidisciplinary approach combining preclinical and clinical research, in collaboration with academic, industrial, health care and public/patient partners, will underpin our future success.


Research Activity Codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;5.1 PHARMACEUTICALS
Health Categories: INFLAMMATORY AND IMMUNE SYSTEM;MUSCULOSKELETAL
Award Title: Pain and motivation: the impact of tonic experimental pain on reward- and effort-based decisions
Funder: The British Academy

Abstract: Pain is important for guiding our behaviour. A child who touches a hot stove, for example, will quickly learn not to repeat that action. Acute pain is thus linked to goal-directed action, but little is known about how pain lasting minutes or hours may influence motivational processes. When pain persists, it might increase comfort or pleasure seeking, inhibit exploratory behaviour, and reduce physical effort. To investigate effects of tonic pain on reward- and effort-based decisions, I will use validated procedures to deliver a safe, extended pain stimulus to healthy human volunteers. Before, during, and after the pain, participants will complete a reward-based reversal learning task to assess reward sensitivity and cognitive flexibility (Experiment 1), or a reward/effort trade-off task to measure physical effort to obtain rewards (Experiment 2). These experiments will provide the first test of whether long-lasting pain has persistent effects on learning and motivation in healthy humans.


Research Activity Codes: 1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health Categories: NEUROLOGICAL
Award Title: Parental Alienation, Domestic Abuse and the Family Courts – a collaborative action research project
Funder: The British Academy

Abstract: Parental Alienation (PA) is an emerging area of scholarship and a highly contested concept. The Children and Family Court Advisory and Support Service describe it as a child’s unjustified resistance towards a parent caused by psychological manipulation by the other parent.  In recent years perpetrators of domestic abuse (DA) are increasingly using allegations of PA against their victims with the aim of negating DA. This research aims to explore how PA is used in, and impacts on, child arrangements cases where DA is an issue, how family courts respond to accusations of PA, and how barriers to safeguarding victims of DA and children can be overcome. This study will adopt a collaborative action research framework involving interviews with victims of DA accused of PA in family court cases. The findings will develop national policy for improving family court responses to DA to achieve safer outcomes for victims and children.


Research Activity Codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;7.1 INDIVIDUAL CARE NEEDS
Health Categories: DISPUTED AETIOLOGY AND OTHER
Award Title: Pass the Wnt, from secretion to signalling
Funder: Wellcome Trust

Abstract: A relatively small number of proteins have been suggested to act as morphogens, molecules that spread within tissues to organize cell fate decisions and tissue repair. Among them are Wnt proteins, which, surprisingly for signalling molecules, are relatively insoluble because of a palmitoleate moiety that is essential for signalling activity. A number of proteins are dedicated to Wnt secretion and transport in the extracellular space. In particular, Wntless escorts Wnt from the ER to the cell surface, and Dlp-class glypicans shield the Wnt lipid in the extracellular space before it engages with signalling receptors of the Frizzled family. We will combine structural, biophysical, and genetic approaches to characterise the key interactions that Wnt proteins and their lipid engage with during this journey. Thus, we will determine how Wnts are released from Wntless in secreting cells and allowed to form a complex with Dlp-class glypicans. We will determine the glycosaminoglycans that support the formation of the Wnt-glypican complex before elucidating the complex’s structure and identifying the key determinants of affinity. These measurements will lead to a mechanistic understanding of Wnts’ extracellular transport and subsequent hand-over to Frizzleds and form the foundation of a realistic mathematical model of Wnt gradient formation.

Lay Abstract: Much like humans in societies, cells in tissues and organs must communicate so that they can coordinate their activities. One common form of cell communication involves secreted proteins that are produced by a subset of cells and spread to surrounding cells, where they bind to surface receptors and trigger changes in gene activity. For cells to work seamlessly together during development and homeostasis, it is crucial that signals spread over the right distance. We are proposing to study this question for a class of signalling proteins called Wnts, which control stem cell behaviour and have been shown to trigger cancer when overactivated. We will map all the interactions that Wnts make in the extracellular space and determine how they ensure that Wnts reach the appropriate cells. With this knowledge, it will become possible to tune the range of Wnt action in the context of regenerative medicine or anti-cancer treatments.

Research Activity Codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health Categories: GENERIC HEALTH RELEVANCE
Award Title: Pathophysiological factors in the diagnosis and treatment of the Guillain-Barre syndromes
Funder: Wellcome Trust

Abstract: 100 years after its first description in 1916, we still know very little about the cause of Guillain-Barre syndrome (GBS) that is characterised by severe paralysis due to inflammation in peripheral nerves. We know the disease is precipitated by a wide range of infections that induce antibodies as part of the normal protective immune response; however in GBS cases, rogue antibodies are made by the immune system that inadvertently attack the nerves due to a mistake in immune programming. Understanding how they do this in the different GBS disease variants, and how to use this information to diagnose and treat GBS is the aim of this proposal. We have developed experimental methods for large scale screening of human GBS blood for abnormal antibodies. We have also developed mouse models based on these screening data that can examine disease pathways in nerve tissues, and test new treatments. Through this translational research, our overall goal is to change the GBS landscape for future patients, health care providers and researchers.


Research Activity Codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health Categories: NEUROLOGICAL
Award Title: Periodontitis and future cognitive decline
Funder: Dunhill Medical Trust

Abstract: Periodontitis is widely known as gum disease; it is a progressive destructive inflammatory condition caused by
dental plaque. Severe periodontitis (SP) is the sixth most prevalent condition in the world. The global age
standardized prevalence of SP in 2010 was 11.2% rising steeply in those aged >65 years. Cross sectional studies
suggest an association with dementia but prospective data are lacking. Between 2001& 2003 men enrolled in
the Prospective Epidemiological Study of Myocardial Infarction (PRIME) in Northern Ireland completed a
Mini Mental State Examination (MMSE). 1400 men with teeth had a periodontal examination. Samples of
dental plaque were collected from 727 men and quantitative PCR for common dental pathogens carried out.
We aim to fully cognitively assess the surviving men and assess if prior periodontitis, genetic risk, presence of
antibodies to common oral pathogens and raised serum levels of proinflammatory cytokines in stored and
fresh blood contribute towards dementia risk.

Lay Abstract: Periodontitis is widely known as gum disease; it is an inflammatory condition caused by bacteria which build
up on the surface of the teeth known as dental plaque. Periodontitis affects large numbers of people; almost
two-thirds of those aged 65 or older have either moderate or severe periodontitis. Studies have suggested it
could increase risk of later dementia. We aim to revisit 1400 men who took part in the Prospective
Epidemiological Study of Myocardial Infarction (PRIME) in Northern Ireland from 2001-2003. All men with
teeth had a periodontal examination, a genetic test and blood stored; samples of dental plaque were collected
from 727 men at this time and we identified what bacteria were present. We aim to carry out a comprehensive
cognitive assessment in all surviving PRIME men, analyse fresh and stored blood and perform a genetic
analysis to ascertain if prior periodontitis increases the risk of dementia.

Research Activity Codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health Categories: ORAL AND GASTROINTESTINAL;NEUROLOGICAL
Award Title: Persistent Infections
Funder: Medical Research Council

Abstract: Understanding the role that viral variation plays in human cytomegalovirus (HCMV) disease has been limited by the large size of the genome and the challenges of getting whole-genome data from patient samples. My group has created a high-throughput pipeline for sequencing complete HCMV genomes directly from clinical material. We plan to capitalise on this by relating the diversity, evolution and strain dynamics of HCMV to clinical outcome in various groups, particularly transplant recipients. This will involve analysing viral genome sequence data from at least 1200 patient samples. We have also used modern genomics and transcriptomics technologies to help establish a particular HCMV isolate (Merlin) as a well characterized research strain for use in laboratory studies. Using Merlin, we plan to determine the functions of HCMV long noncoding RNAs (lncRNAs), in order to assess whether they provide points at which HCMV infections might be suppressed. This will involve detailed functional characterization of viral mutants with completely characterised genomes. Finally, we plan to provide added value to the congenital, genital and transplant-acquired infections programme by developing a pipeline for sequencing human herpesvirus 6 (HHV6) genomes. This will contribute to understanding the evolution and function of inherited chromosomal integration by this virus in human populations, on which evidence for clinical relevance is starting to accumulate from population studies.


Research Activity Codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health Categories: INFECTION
Award Title: Personalised adjunctive anti-inflammatory therapy to reduce deaths from tuberculosis.
Funder: Wellcome Trust

Abstract: Tuberculosis kills more people worldwide than any other single bacterial infection but its clinical consequences and response to treatment are highly variable. Why people respond differently to tuberculosis treatment is unknown, but the identification of markers that predict response could lead to personalised and more effective treatment. Tuberculous meningitis kills around 30% of sufferers. Previously, we showed tuberculous meningitis deaths were reduced by anti-inflammatory steroid treatmen t, but not everyone benefited. Whether steroids reduce deaths in HIV-infected patients was unclear; and we discovered a gene (called LTA4H) which controls tuberculosis inflammation and appeared to predict steroid benefit. Patients over-expressing the gene suffered high inflammation and benefited greatly from steroids; patient under-expressing the gene had low inflammation and did not benefit from steroids. We will perform trials in Vietnam and Indonesia to determine whether steroid-induced surv ival from tuberculous meningitis can be predicted by the LTA4H gene and HIV infection. We will look for other survival predictors and we will investigate whether any of them influence severity and response to treatment in patients with lung tuberculosis, the commonest form of tuberculosis. Our aim is to show tuberculosis deaths can be reduced, especially from the most severe forms, by personalising therapy.


Research Activity Codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health Categories: INFECTION