NIHRDataInsights/HRCSData huggingface dataset:
Award Title: AI-enabled Portable Incontinence Management Device
Funder: Economic and Social Research Council

Abstract: Our primary target within this project is to create prototypes of an portable incontinance management device while continuously engaging with all the stakeholders. We expect the instrumented sock, and the associate AI algorithm will be ready for clinical validation by the end of the project. The technical aspect of the project will have three distinct sub-themes.

-Material design of the sock and the embedded electrodes
-Design of the miniaturized stimulation electronics connected to the sock
-Development of the associated AI algorithms displayed on a mobile/web application

Lay Abstract: An overactive bladder is a common medical condition, particularly among the elderly. It leads to urinary incontinence (UI) and influences the quality of life for around 40% of those above 75 (>6million people in UK). People often consider this as a natural progression to old age and do not actively seek any treatment. However, UI is one of the main factors why the elderly lack confidence and give up their independence to move to care homes.  

Conventional approaches to treat UI, e.g., drugs and bladder-catheterisation have several side effects (e.g., dry-mouth, constipation, confusion). Invasive electrical stimulation of the Tibial nerve (around the ankle) is an established alternative treatment. But a needle electrode inserted into the leg can be painful and distressing. Recently, a non-invasive version of this method has been demonstrated to be successful for older adults. However, it comprises multiple hospital visits per week over a duration of 2 months. Such a long treatment process leads to reduced adherence especially for the frail elderly who have already accepted UI to be a part of their life. 

We propose an instrumented sock that the user can wear comfortably throughout the day, while electrodes weaved into it will stimulate the tibial nerve when necessary. The stimulation parameters will use an AI-based algorithm (via a smartphone) set by the clinician. The proposed system can be tried by a larger section of the population without surgery or repeated hospital visits. Hence, users will have much greater privacy and flexibility in managing incontinence.

Research Activity Codes: 5.3 MEDICAL DEVICES
Health Categories: RENAL AND UROGENITAL
Award Title: AI-powered next-generation imaging biomarkers for dementia
Funder: Medical Research Council

Abstract: The vision of this project is to accelerate the translation of next-generation imaging biomarkers of dementia from academic research into real-world impact. The need for advanced biomarkers of dementia has never been greater, as treatment that slows or stops the disease remains elusive. Recent high-profile trial failures underscore the importance of identifying the right participants for trials - those for whom the disease is at an early enough stage to benefit from potential treatments. Biomarkers with higher sensitivity are vital for this endeavour. This project will contribute to this very effort by expediting the process of delivering cutting-edge imaging biomarkers uncovered in academic research to the frontline of therapeutic trials. The project objective will be achieved through a close collaboration between AInostics, an award-winning imaging AI start-up, and University College London (UCL), an international leader in the development of novel imaging biomarkers for dementia and neurodegenerative diseases generally. The close collaboration will be built through the proposed secondment of an early-career imaging researcher, Dr Michele Guerreri, who has recently developed a cutting-edge imaging biomarker sensitive to subtle changes resulting from neurodegeneration. The secondment will give him the ideal opportunity to turn his novel research idea into a viable commercial product, enabling its expedited translation into frontline applications. Crucially, joining the rank of innovation scholars will allow Dr Guerreri the time and space to gain the essential knowledge, and to develop the necessary skills, to successfully operate at the interface of academic research and commercial development in the future. In the long term, this invaluable experience will position him to play a key role in facilitating the interactions between UCL and the UK's vibrant imaging AI sector, expediting the impact of public investment on making UK a healthy and prosperous nation.


Research Activity Codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health Categories: NEUROLOGICAL
Award Title: AMPA Receptor Biogenesis, Structure and Function
Funder: Medical Research Council

Abstract: AMPA glutamate receptors (AMPARs) are main mediators of excitatory neurotransmission and are central to synaptic plasticity, a process underlying learning. AMPARs are also essential for brain development and their dysfunction contributes to various neurological diseases, rendering them a potential drug target. Neuronal AMPARs are composed of four pore-forming subunits and different types of auxilliay subunits, that are expressed in diverse, partly overlapping patterns in the brain. The precise composition of the AMPAR comlex is essential for post-synaptic signal processing and determines, signalling properties, trafficking to/from synapses and synaptic nano-positioning of the receptor. Our research aims to: 1) unravel mechanisms underlying gating transitions of major AMPAR signaling complexes at the atomic level, and 2) reveal AMPAR organisation at synapses, at the nanoscale.  Our ultimate aim to understand the central role of the AMPAR complex in information storage and learning. In aim 1, we use a combination of cryo-EM, molecular dyamics (MD) simulations and patch-clamp electrophysiology to study gating control of recombinant AMPAR complexes that closely resemble predominant assemblies found in the forebrain. Increased resolution of the ion transduction sector has allowed us to locate traversing cations, as well as study the role of lipids and allosteric modulators. In combination with MD simulations and single-channel recordings, our structural data are expected to generate a detailed understanding of the gating machinery and its regulation by auxiliary subunits. This work is being followed by cryo-EM analysis of native AMPAR extracted from neuronal synapses of select circuitries, permitting us to capture the architecture and complex stoichiometry of synaptic AMPARs.  For aim 2, we have shown that the sequence-diverse AMPAR N-terminal domain (NTD), which faces the synaptic cleft, is essential for receptor anchoring at postsynaptic sites and that deletion of the NTD impedes synaptic potentiation. Our data revealed that this domain provides a synaptic anchor positioning the receptor opposite presynaptic glutamate release sites. This organisation is expected to be essential for efficient signal transmission and synaptic potentiation. Inherent to this model is the unique conformational freedom of the modular AMPAR extracellular region, permitting NTD interactions with synaptic cleft proteins, which we are currently identifying in BioID screens.  To study the organisation of AMPARs at synapses at the nanoscale, we have implemented 3D-stochastic optical reconstruction microscopy (3D-STORM) together CRISPR/Cas9 tagging of endogenous AMPARs in brain tissue. This set-up will ultimately allow us to follow AMPAR dynamics (and NTD-mediated positioning) at synapses undergoing potentiation with high precision.


Research Activity Codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health Categories: NEUROLOGICAL
Award Title: ASTFOX: A Phase I study of the IAP antagonist, ASTX660, in combination with standard of care FOLFOX chemotherapy in metastatic colorectal cancer
Funder: Cancer Research UK

Abstract: Background:  Cytotoxic chemotherapies remain the mainstay of treatment of metastatic colorectal cancer (CRC) with an unmet need to improve treatment given the typical low response rates of chemotherapy in the second line treatment setting. Inhibitor of Apoptosis Proteins (IAPs) are frequently deregulated in cancer, and are a major contributor to chemo-resistance through apoptotic inhibition and pro-survival NF-kappaB signalling. Restoration of apoptotic function through inhibition of IAPs is an attractive therapeutic strategy with additional potential for enhanced cell death through immunomodulation of the tumour microenvironment. ASTX660 is a dual antagonist of both XIAP and cIAP1 and has been evaluated as a single-agent with a recommended phase II monotherapy dose (RP2D) and schedule identified. Our pre-clinical data have shown enhanced cell death in vitro and tumour growth inhibition in vivo following treatment with oxaliplatin/5FU (FOLFOX) chemotherapy and ASTX660. A phase I trial combining ASTX660 and FOLFOX in metastatic CRC is warranted.    Patient population:  Histologically proven metastatic CRC where FOLFOX chemotherapy would be an appropriate second line treatment option. Additional eligibility criteria include: RECIST measurable and biopsiable disease; adequate organ function and performance status 0-1.    Aims:  The primary aims are to assess the safety and tolerability and to determine the maximum tolerated dose (MTD) and RP2D of ASTX660 in combination with FOLFOX.  The secondary aims are to determine the pharmacokinetics of ASTX660 in combination with FOLFOX and to preliminarily assess the anti-tumour activity of the combination.   There are additional exploratory aims which include investigating the effects of combination therapy on changes in apoptotic markers and immune cell infiltrate in tumour biopsies.    Methods:  Up to 30 patients will be recruited. The mTPI-2 (keyboard design) will be used to find the MTD. The target toxicity rate for the MTD is 0.25, with the acceptable toxicity probability interval of (0.2,0.3). Patients will be enrolled and treated in cohorts of size 3 across five pre-defined dose levels. Patients will receive combination ASTX660 (at cohort-assigned dose) and FOLFOX up to a planned 12 cycles (each of 14 days duration).     Use:  If this study demonstrates that the combination of ASTX660 and standard care chemotherapy can be delivered safely and is well tolerated by patients with metastatic colorectal cancer, then formal assessment of clinical efficacy will be needed to incorporate this therapy into routine clinical practice. This may be guided by any efficacy signal observed in this study.


Research Activity Codes: 6.1 PHARMACEUTICALS
Health Categories: CANCER AND NEOPLASMS
Award Title: Adaptive decision templates in the human brain
Funder: Wellcome Trust

Abstract: Interacting with the surrounding environment depends on our ability to extract meaningful patterns from incoming streams of sensory information. Learning and experience are known to facilitate this skill; yet, we know little about how the brain extracts structure and generalises this knowledge to novel settings. Here, I propose to test the brain mechanisms underlying structure learning using contrasting tasks that involve learning structure in space vs. time at different levels of complexity (simple vs. complex feature contingencies). I will use computational modelling to interrogate the processes involved in learning behaviourally-relevant structures (i.e. decision templates). I will relate this system-level insight to multimodal neuroimaging to provide converging evidence for brain mechanisms that mediate learning specialisation and generalisation. I will exploit high-field imaging to test fine-scale decision templates in the visual cortex. I will combine 7T imaging with human electrophysiology (MEG/EEG) and interventions (TMS) to test for local and larger-scale brain circuits that retune decision templates through feedback and inhibitory interactions. Finally, I will test whether these mechanisms support our ability to generalise previous experience to novel contexts and tasks. This integrated approach will advance our understanding of the brain’s capacity for adaptive and resilient behaviour with implications for promoting lifelong learning.

Lay Abstract: When immersed in a new environment (e.g. navigating a new city or being surrounded by speakers of an unknown language) we are challenged to make sense of an initially incomprehensible stream of events. At first, it seems like a befuddling cacophony that leaves us completely unprepared for what will happen next. And yet, quite rapidly, the brain finds structure and meaning in the incoming signals, helping us to predict and prepare ourselves for future actions. We have little understanding of how the brain achieves this. Here, I propose to study participants’ ability to learn different types of structure (i.e. regular patterns in clutter or sequences). Using sophisticated algorithms, we will track participants’ ability to extract structure during training. Our goal is to test how these changes in behaviour relate to underlying brain changes. We will use cutting-edge brain imaging methods, to provide complementary evidence for the brain mechanisms that support structure learning. We will test how different brain circuits: i) specialise to support learning of spatial vs. temporal structures, ii) interact to support our ability to generalise knowledge about structure to new contexts. In the longer term, harnessing the brain’s capacity for learning has potential implications for boosting lifelong training.

Research Activity Codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health Categories: MENTAL HEALTH;NEUROLOGICAL
Award Title: Added value and resilience
Funder: Biotechnology and Biological Sciences Research Council

Abstract: Food and nutrition security requires safe access to affordable and nutritious food supplies. We aim to enhance grain quality for human health, combat non-communicable diet-related diseases and improve the resilience of wheat production systems to biotic stresses. We will address two topics, with shared objectives across the Desiging Future Wheat BBSRC Strategic Progamme (DFW) and other Rothamsted Research, John Innes Centre, Earlham Institute, Quadram Institute Bioscience and NIAB programmes. Both exploit previous BBSRC investments in germplasm resources and the latest genomic developments, to understand and manipulate the genes and pathways defining wheat grain composition and host resistance/susceptibility to pathogens/pests. We will dissect a range of traits exploiting the germplasm and other resources developed within DFW. These traits include resistance to a range of pathogens and pests (such as rusts, Zymoseptoria, Fusarium, take-all, mildew, eyespot and aphids) and finally the quantity and quality of starch, dietary fibre and minerals in grain.


Research Activity Codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS
Health Categories: CANCER AND NEOPLASMS;CARDIOVASCULAR;METABOLIC AND ENDOCRINE;ORAL AND GASTROINTESTINAL;STROKE
Award Title: Addressing Child and Adolescent Musculoskeletal Pain: the CAM-Pain Programme
Funder: Versus Arthritis

Abstract: Musculoskeletal pains, such as back or knee pain, are common throughout the life course, and are a leading cause of disability worldwide. However, musculoskeletal pain research among children and adolescents is scarce. We know very little about how many children visit doctors about musculoskeletal pain, what diagnoses and treatments children get, how many children have persistent pain problems, and what can help doctors identify who will get better and who might not.

Professor Kate Dunn and her team will use anonymized national medical health records to answer all of these questions. The researchers will then work with children aged 8 – 18 years, parents, and healthcare professionals to co-develop a support package for children and parents about musculoskeletal pain. They hope that age-appropriate information available as leaflets, cartoons, videos or other formats, will help children and their parents to understand pain and ways of managing it. This self-management support package will be tested and improved with the help of children and parents within a healthcare setting. This award will provide new information on primary care services for musculoskeletal pain (Versus Arthritis Pain Roadmap priority 9), produce a support kit to aid management (priority 7) and, through a life course perspective, work towards the prevention (priority 11) of musculoskeletal pain in children and adolescents (an under-represented group; priority 4).

Impact: Children and adolescents with musculoskeletal pain, their families, clinicians, researchers and policymakers will all benefit from the outputs of this award. The data generated in the first part of this project on prevalence, incidence, trends, management, prognosis and prognostic factors for child and adolescent musculoskeletal pain will be of significant value for further research and policy use. The CAM-Pain (Child and Adolescent Musculoskeletal-Pain) support kit will provide much_x0002_needed information and support for an under-served group.


Research Activity Codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health Categories: MUSCULOSKELETAL
Award Title: Adjunctive Ivermectin Mass Drug Administration for Malaria Elimination: A cluster randomized trial
Funder: Medical Research Council

Abstract: This trial will be the first to investigate the impact of adjunctive IVM MDA to reduce malaria transmission in a seasonal low-transmission setting. Adjunctive IVM MDA will be compared to DP-only MDA (with treatment daily for three days during the three months of peak malaria transmission (July-September)) in combination with standard programmatic interventions (long-lasting insecticidal nets (LLIN) and intermittent preventative treatment in pregnancy (IPTp)) in a cluster-randomized community-based trial. Primary outcome measures will be population-based Pf prevalence (estimated using ultra-sensitive PCR) and Anopheles gambiae survival (measured using parity). Data on MDA coverage, acceptability and feasibility of the intervention and a cost-effectiveness analysis will be included. We have established field infrastructure on the Bijagós Archipelago (including trained field entomologists and field laboratory technicians) and have detailed recent baseline data on malaria and NTD epidemiology and vector populations on the islands. This island setting provides an unparalleled opportunity to understand transmission and its interruption using a combined MDA strategy through investigating the impact of imported infections (through an expanded community-based CDSAT (case detection screen and treat) intervention in both arms), using serological markers to define transmission dynamics and estimate entomological inoculation rate (EIR) and monitoring the effect of IVM MDA on confined vector populations over time (parity, sporozoite rate, resistance to pyrethroids and IVM and population genomic diversity).


Research Activity Codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS;6.1 PHARMACEUTICALS
Health Categories: INFECTION
Award Title: Adult onset Type 1 Diabetes: Are Slow Progressors and Late Starters examples of immune regulators?
Funder: Diabetes UK

Abstract: Approximately half of type 1 diabetes is diagnosed in adults and a recent study of genetic risk suggests that 10% of adult diabetes has an autoimmune aetiology. Could these individuals represent examples of natural immune regulation? For children developing multiple islet autoantibodies, the risk of clinical diabetes is 84% by 15 years old. However, progression from islet autoantibodies to clinical disease can take decades in some individuals. If most childhood cases of autoimmunity develop diabetes by their mid-teens, where do cases of adult type 1 diabetes come from?  Are these individuals “Slow Progressors” from childhood islet autoimmunity, or “Late Starters”, with autoimmunity beginning in later life?

We have identified 132 “Slow Progressors” from several international studies, but these individuals are too rare to account for all cases of adult type 1 diabetes.  This project aims to characterise individuals who seroconvert to islet autoimmunity over the age of 10 years. Humoral immune response, genetic risk, and CD4 T-cell and B-cell activity will be determined in these “Late Starters” and compared between Slow Progressors, controls without diabetes, and patients with diabetes. Research into the heterogeneity of type 1 diabetes could help identify therapeutic targets to slow or prevent disease.


Research Activity Codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health Categories: METABOLIC AND ENDOCRINE
Award Title: Advanced photomanipulation microscopy at the Cambridge Advanced Imaging Centre
Funder: Wellcome Trust

Abstract: The Cambridge Advanced Imaging Centre (CAIC) is a research facility in the School of Biological Sciences at the University of Cambridge. Since opening in 2013, physical scientists at CAIC have worked with biologists to bring online several new and unique microscopes which are now utlised by over 100 research labs from 16 Departments.
 
While pushing the frontiers of imaging technology, we have identified a critical lack in the ability to perform photomanipulation experiments combined with fast imaging. These experiments include optogenetics, photoactivation, ablation or bleaching specific regions of cells or parts of cells, sometimes deep in tissues, whilst imaging in real time from millimetre to nanometre scales. Research that will benefit from this technology spans multiple departments and a diverse range of groups, including many Wellcome Trust funded researchers.
 
We are requesting resource to develop an advanced microscope capable of a wide range of manipulation and imaging modalities. This technology will require three major components: adaptive optics for fast shaping of light; extensive range of lasers to enable exploitation of existing and emerging fluorophores and the newest generation of spinning disk confocal unit with cameras for fast and and low photon number imaging.

Lay Abstract: The Cambridge Advanced Imaging Centre (CAIC) is an imaging facility in the School of Biological  Sciences at the University of Cambridge. Since it opened in 2013, physicists and  computing scientists at CAIC have worked with biologists to develop new and exciting microscopes to enable the fastest and highest resolution imaging possible.

Scientists working with CAIC now wish to perform experiments where light is used to perturb or modify specimens being imaged in real-time. Such experiments require exquisite accuracy in manipulation and high speed imaging to observe the effects. Researchers excited about using these tools span a wide range of departments here at Cambridge including Genetics,  Zoology and Physiology, Development  &  Neuroscience.

This application requests resource to develop an advanced microscope capable of sculpting light in 2D and 3D for the greatest flexibility in photomanipulation and imaging.

Research Activity Codes: 1.5 RESOURCES AND INFRASTRUCTURE (UNDERPINNING)
Health Categories: GENERIC HEALTH RELEVANCE