NIHRDataInsights/HRCSData huggingface dataset:
Award Title: Affordable near-patient diagnostics to distinguish infectious diseases in the Philippines (AND2ID in Ph)
Funder: Medical Research Council

Abstract: Infectious diseases are a major cause of morbidity and mortality in the Philippines. Patients may present with fever and a wide range of non-specific symptoms, which are difficult to diagnose without specialist laboratory tests. Dengue is a major public health problem in the Philippines, and is endemic in all regions of the country. Leptospirosis is also endemic and may be misdiagnosed as dengue due to similarity in early clinical manifestations. Current diagnostic tests that rely on culture of pathogens or detection of raised antibody titres can take days to weeks to provide actionable results, and are too slow to guide initial patient management. In the first week of infection, nucleic acid testing (NAT) is the most reliable method to identify the causative agent, but these are expensive and usually require well-resourced laboratories. The aim of this project is to create innovative low cost diagnostics, using local resources and show whether reduction in cost of a diagnostic has an impact on the ability to target treatment (including antibiotics) and lessen the impact of febrile illness on the patient, society and the economy. The project has three steams: (1) Technological Innovation, (2) Clinical study, (3) Economic modelling and will result in  - Laboratory evaluation of a new NAT reagent in UK and Philippines  - Clinical trial of of the new test in Philippines with impact analysis of the clinical pathway.  - Development of an affordable diagnostic NAT platform design with prototype production for trials in a rural clinical site in Philippines for dengue and leptospirosis. - Cost-effectiveness analysis and healthcare economics model of diagnostic platforms.  - Impact analysis of diagnostics on patient pathway.


Research Activity Codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health Categories: INFECTION
Award Title: AlCohol use in HumanitariAN settings: a programme of work to address alcohol and associated adversities among conflict-affected populations in UGanda and UkrainE (CHANGE)
Funder: Wellcome Trust

Abstract: Conflict-affected populations across the world are vulnerable to alcohol misuse and psychosocial distress. This is a direct consequence of exposure to war, violence, and ongoing stressors in their new areas of settlement such as impoverishment, unemployment, and discrimination. Alcohol may be used as strategy to cope with adversities which refugees and internally displaced people might face, and may cause or result from psychosocial distress. Despite the major health, social and economic consequences of alcohol misuse, there is a notable absence of interventions addressing alcohol use disorders (AUD) among conflict-affected populations. This proposal seeks to complement a WHO evidence-based psychological intervention for people living in adversities (“Problem Management Plus” (PM+)) with strategies to reduce alcohol misuse, thereby developing an intervention which prioritises alcohol misuse but also addresses other underlying mental health problems of conflict-affected populations. We will develop our intervention called PM+/AUD through a comprehensive formative research process, and evaluate the final intervention through two independent randomised controlled trials among South Sudanese refugees living in Uganda, and internally displaced persons in Ukraine. Our project will include social science research on implementation and scaling-up, and will produce guidelines for the treatment of AUD among conflict-affected populations.

Lay Abstract: Research has shown that internally displaced persons and refugees are vulnerable to poor mental health and alcohol misuse leading to harmful drinking patterns and alcohol use disorders. In response to the large number of people with mental health problems in resource poor areas, the World Health Organization has developed a short psychological therapy called Problem Management Plus (PM+). PM+ is a very effective psychological treatment, however, it does not address alcohol misuse, a major problem among conflict-affected populations. Our research group aims to fill this gap and will develop the first evidence-based psychological therapy addressing alcohol misuse for this population group. We will base our alcohol intervention on PM+, and will test and evaluate our new intervention among South Sudanese refugees living in Uganda, and internally displaced persons in Ukraine.

Research Activity Codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health Categories: MENTAL HEALTH
Award Title: An Investigation into Emotional Health in Outer-Space: A Pilot Study
Funder: The British Academy

Abstract: Astronauts experience poor mental health despite their military grade training. In this project we investigate why poor mental health persists in space-work using a novel combination of critical, social and emotion theory. We focus on emotional health because it is missing from space research as well as the cognate field of systems science which has recognised the importance of emotion. Emotional health is fundamental to mental health and cognitive function. We propose a humanistic, critical examination which investigates the organisational, social, systemic and technical conditions that constrain and enable space travellers’ emotional health. We will conduct primary research comprised of interviews with space programme participants. This project will impact current debates on emotional health in space and also draw implications for mental health in similar extreme environments by developing a group of researchers and stakeholders, publications, knowledge dissemination and outreach events.


Research Activity Codes: 7.1 INDIVIDUAL CARE NEEDS
Health Categories: MENTAL HEALTH
Award Title: An innovative cell analytics technology that can increase therapy manufacturing efficiency by 30% and therefore reduce costs for up to 400K UK patients per year
Funder: Innovate UK

Abstract: Cytomos is a UK biotechnology SME with a core project team of Lindsay Fraser (CSO, Head of Research/Programme Manager), Gordon Sharp (CTO, Instrument Development), Tom Clayton (Lead System Architect, Firmware/Software Development) and Sevi Giakoumelou (Project and Research Manager, Research Development).



The cost of cell therapy for genetic disorders and rare diseases can be staggering, ranging from £40K to well over £1M, with some treatments continuing for a lifetime. This level of expense can put care out of reach for some populations and has created an immediate and urgent need for more efficient cell and gene therapies to ensure that personalised medicine is not limited by socioeconomic factors. The UK is home to over 12% of the world's clinical trials for cell and gene therapy, and to increase efficiency, the UK's Biomanufacturing Technology Roadmap calls for a 90% reduction in manufacturing costs and an 80% reduction in time by 2030\.



Existing cell therapy manufacturing processes use techniques that do not look directly at the cells during manufacture and thus return limited information. To create more effective analytics, Cytomos is developing technology that looks at the details of an individual cell, using electrical fields to create a label-free, scalable solution with automation potential that could benefit up to 400K UK patients per year, addressing healthcare inequality.



Cytomos' project will increase cell therapy manufacturing efficiency by 30% and reduce patient costs by up to 20%. A streamlined manufacturing process will reduce environmental impact and further improve availability to patients.


Research Activity Codes: 5.2 CELLULAR AND GENE THERAPIES
Health Categories: GENERIC HEALTH RELEVANCE
Award Title: An innovative, interdisciplinary platform for the dissection of Pneumocystis, a deadly fungal pathogen of humans
Funder: Medical Research Council

Abstract: Pneumocystis jirovecii is an opportunistic pathogen causing life-threatening pneumonia in immunocompromised patients and it colonizes the lungs of healthy infants. The worldwide incidence of Pneumocystis pneumonia exceeds 400,000 cases per year with mortality rates of 20 - 80%. This is a serious problem for developing countries where the population of HIV-infected individuals is over 6 times that in developed countries. Challenge: The inability to culture Pneumocystis in vitro despite 3 decades of research makes this pathogen uniquely difficult to study. Diagnosis and treatment of Pneumocystis infections has relied primarily on microscopic detection in respiratory specimens. The lack of in vitro culture methods has been recognized as the major obstacle in Pneumocystis research.  Recent genome sequencing has identified a potential explanation for the inability to culture Pneumocystis: it has an extremely reduced genome that lacks essential metabolic pathways. This has prevented growth independently of its mammalian host. Pneumocystis has developed unique dependencies on the host for nutrients as well as highly efficient strategies to evade the host's innate and acquired immune defences. Thus, intimate host-fungus cross-interactions are essential for growth of the pathogen, and simple supplementation of growth media to overcome predicted auxotrophic requirements has not been sufficient to solve the problem. Principal hypothesis: The metabolic issue is more subtle: the pathogen also relies on the host to maintain redox and/or energy homeostasis.  Innovative approach to resolve this issue: I will develop an in silico metabolic model of Pneumocystis growth and metabolism based on new genomic data. Outcomes: This work will release a critical bottleneck in Pneumocystis research, and provide major insights into the co-evolution of Pneumocystis pathogens with their mammalian hosts.


Research Activity Codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT;2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY)
Health Categories: INFECTION
Award Title: An integrated systems-level framework for deciphering multidrug resistant epilepsy.
Funder: Medical Research Council

Abstract: Epilepsy is a common, serious neurological disease - it is the 5th most disabling disorder in the WHO's rankings of disability by illness and accounts for 3% of all A&E attendances in the UK NHS. The greatest burden falls on the 20-30% with multidrug resistant epilepsy (MDRE). There has been little progress in improving seizure control in the last 50 years of antiepileptic drug development and none of the current drugs are disease modifying or curative. This absence of progress despite decades of research mandates a new scientific approach. Systems-biological analyses provide powerful techniques for elucidating molecular processes and pathways underlying complex disease. In particular, we have established proof-of-concept for the use of gene regulatory network (regulome) approaches to new drug discovery, including the discovery of novel patented drugs and targets using these approaches. The recent development of methods to assay the transcriptomes of individual cells (single cell RNA-sequencing, scRNA-seq) now offers the opportunity to rapidly accelerate this progress by incorporating cell-type and disease-context specificity to our therapeutic predictions. In this application we start from the hypothesis that connecting genomic liability for MDRE to cellular transcriptomes of the human epileptic brain will identify cell-types and pathways fundamental to the genesis MDRE. Taking an integrative approach, we first evaluate how genomic loci implicated in susceptibility to MDRE map onto specific cell-types, gene networks and functional pathways and then, using knowledge of the cell-types and pathways perturbed in MDRE, we apply a cell-type specific regulome framework to the discovery of new druggable targets for MDRE. Our project has the potential to rapidly advance the discovery of new drugs for treatment resistant epilepsy, and will provide fundamental insights into cell variability and cell-type specific gene expression in the human brain in health and disease.


Research Activity Codes: 5.1 PHARMACEUTICALS
Health Categories: NEUROLOGICAL
Award Title: An investigation as to whether transposable element expression drives placental inflammation.
Funder: Borne

Abstract: One risk factor of preterm birth are infections, which can be partly kept at bay by innate immune responses within the placenta. Evidence suggests that it is the inflammation that is triggered by such immune responses that induces preterm birth. Moreover, infections alone cannot account for majority of preterm births. We hypothesize that inflammation could also be triggered by components of our own genome termed transposable elements (TEs). When active, TEs can trigger anti-viral responses that lead to inflammation, as shown previously in cancer and ageing. TEs are normally repressed through a number of so-called epigenetic mechanisms, which prevent those parts of the genome from becoming active.
We posit that alterations in epigenetic mechanisms can lead to TE activation and 
inflammation in the placenta. We will test this hypothesis by using placental cells in culture and removing key components of the epigenetic machinery. We will ask whether these manipulations drive TE activation and consequently an anti-viral-like response. We will also ask if some placental samples from a large collection of pregnancies show concomitant TE activation and inflammation. These experiments aim to build the evidence base for a larger study looking into the potential role of TEs in preterm birth.

Lay Abstract: One risk factor of preterm birth are infections, which can be partly kept at bay by innate immune responses within the placenta. Evidence suggests that it is the inflammation that is triggered by such immune responses that induces preterm birth. Moreover, infections alone cannot account for majority of preterm births. We hypothesize that inflammation could also be triggered by components of our own genome termed transposable elements (TEs). When active, TEs can trigger anti-viral responses that lead to inflammation, as shown previously in cancer and ageing. TEs are normally repressed through a number of so-called epigenetic mechanisms, which prevent those parts of the genome from becoming active.
We posit that alterations in epigenetic mechanisms can lead to TE activation and 
inflammation in the placenta. We will test this hypothesis by using placental cells in culture and removing key components of the epigenetic machinery. We will ask whether these manipulations drive TE activation and consequently an anti-viral-like response. We will also ask if some placental samples from a large collection of pregnancies show concomitant TE activation and inflammation. These experiments aim to build the evidence base for a larger study looking into the potential role of TEs in preterm birth.

Research Activity Codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health Categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Award Title: An investigation of heat stress in pregnant subsistence farmers
Funder: Wellcome Trust

Abstract: Climate change is one of the major threats to human life as we know it. The effects of climate change are mostly felt by the poorest in the world and in particular by women. Pregnancy is a vulnerable time for women and when pregnant women are exposed to high temperatures, this can effect pregnancy outcome and lead to premature births, low birth weight infants and stillbirths. The underlying cause that results in these poor outcomes is not known. We will study pregnant subsistence farmers in rural Gambia who are exposed to high temperatures when they work in the field. We will monitor them and their fetuses throughout their work in order to identify factors that can be linked to poor birth outcomes. The results will help to identify those women who are at risk and to understand why some women have problems whilst others do not. We will also test simple sustainable options for relieving heat strain for these women.


Research Activity Codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health Categories: REPRODUCTIVE HEALTH AND CHILDBIRTH;GENERIC HEALTH RELEVANCE
Award Title: An investigation of multisensory body representation in fibromyalgia and testing a possible intervention
Funder: Versus Arthritis

Abstract: Fibromyalgia is a debilitating condition characterised by intractable widespread musculoskeletal pain. The causes are unclear but scientific data indicates that aberrant brain processing of bodily signals is linked to a range of chronic pain conditions, and there is some evidence for altered multisensory body representations also in fibromyalgia. A number of recent papers have shown that body illusions, some of them induced via virtual reality, can reduce chronic pain, but none of these have assessed the longevity of pain relief. VR treatment may be particularly suitable for fibromyalgia, given the nature of widespread pain patients experience.To assess this we will test two multisensory full body illusions on patients with fibromyalgia. In the first two years of the project we will investigate whether these full-body illusions can cause sustained reductions in abnormal pain sensations. If we find that the pain-relieving effects of one ~ 2- 5 minute session lasts for at least a day this project would be a first step towards developing a feasible intervention for use by clinicians or by patients at home, and hence be developed as a potential treatment for patients with fibromyalgia. We will also for the first time, explore and quantify the multisensory representation of the body and surrounding space (peripersonal space; PPS) in fibromyalgia, with our final experiment (3) in the third year. We propose that the defensive function and spatial extent of the PPS may be enhanced in fibromyalgia, reflecting adaptation to threats of harm or pain. Hence, we predict that PPS may reflect the sense of vulnerability in patients with fibromyalgia, driven by the fear of threats from the physical or social environment. We will also investigate whether abnormalities in PPS are linked to worse symptoms in fibromyalgia. As a whole, this project will deepen our understanding of how brain representations of the body are altered in fibromyalgia and will test whether these brain representations could be manipulated and targeted by a potential intervention that could help alleviate pain.


Research Activity Codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;5.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health Categories: MUSCULOSKELETAL
Award Title: Analysis of cytomegalovirus pathogenesis in a human challenge system
Funder: Wellcome Trust

Abstract: Our research has made major contributions to understanding the natural history and pathogenesis of human cytomegalovirus (HCMV) in allograft recipients. Critically, we have demonstrated that biomarkers can be applied to stratify patients most at risk of HCMV disease and thus inform clinical practice to reduce HCMV end-organ disease. This clinical approach of administration of antivirals to individuals with elevated viraemia above designated levels provides a unique opportunity to gain fundamental insight into disease processes in a human challenge model of HCMV infection. A multi-disciplinary consortium has been recruited to apply next generation DNA sequencing, molecular virology and functional immunological assays to identify virus and host cell determinants of disease susceptibility. Whole genome sequencing of virus in organ donors (live and cadaveric) and recipients will be used to track the source, replication kinetics and evolution of HCMV strains in seronegative and seropositive recipients. We will then define in vitro humoral, cell-mediated immunity and natural killer responses against HCMV that correlate with protective immunity against primary infection, reinfection and reactivation in these patient groups. This approach has the potential to provide unique insights into the natural history and pathogenesis of HCMV and identify innovative therapeutic approaches against it.

Lay Abstract: Immunosuppressive drugs that prevent the rejection of transplanted organs also reduce immune responses that normally protect patients from virus infections. With previous Wellcome Trust support, we pioneered a way of detecting the most important virus (human cytomegalovirus; HCMV) in the blood to identify those at risk of disease. Based on our research, prompt administration of antiviral drugs at the first detection of HCMV (pre-emptive therapy) was introduced into clinical practice and reduced the serious diseases caused by this virus.
 
These patients all receive the same immunosuppressive drugs, but only some have HCMV detectable in the blood, showing that they have poor immune control of HCMV. This phenotype could be explained if there were genetic differences in some strains of the virus. We will exploit recent changes in contemporary medical practice that mean samples can now be obtained from donors. We have assembled a multidisciplinary team to assess how HCMV evolves after transplant from one person to another and relate the results to measures of how active different components of the immune system are against HCMV. As with our earlier research, we expect the results will explain the phenotypes observed and find immediate practical applications in the management of patients.

Research Activity Codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health Categories: INFLAMMATORY AND IMMUNE SYSTEM;INFECTION
Award Title: Anatomy, acoustics, and the individual: investigating inter-speaker vocal tract variation for forensic speaker comparison
Funder: The British Academy

Abstract: Every person’s vocal tract is unique. Information about its shape is encoded in the speech signal and provides cues for speaker identification. Understanding this encoding is essential for forensic speaker comparison across different speech recordings, but currently there is no direct evidence of how vocal anatomy affects the speech signal. This project addresses the issue with three research questions: which anatomical features contribute most to systematic variation in speech; what is the range of variation of these features within the population; and to what extent are anatomically-derived differences in speech detectable by humans and automatic systems? These questions will be addressed with a novel combination of acoustic modelling and magnetic resonance image analysis. Results will impact forensic casework by highlighting discriminatory features, measuring their impact on listeners, and providing population data. Furthermore, understanding the links between anatomy and acoustics has impact for speech and language therapy and speech synthesis applications.


Research Activity Codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health Categories: EAR