NIHRDataInsights/HRCSData huggingface dataset:
Title: Persistent Fatigue Induced by Interferon-alpha: A New Immunological Model for Chronic Fatigue Syndrome
Funder: Medical Research Council

Abstract: We propose to model chronic fatigue syndrome (CFS) by studying patients taking interferon-alpha (IFN-alpha) for chronic viral hepatitis C (HCV) infection. IFN-alpha treatment leads to acute fatigue in the majority of patients. Most importantly, a proportion of patients continue to experience persistent fatigue, together with other CFS-like-symptoms, for many months after the cessation of treatment, that is, in the absence of the pro-inflammatory stimulus. This phenomenon strikingly resembles CFS, which also persists after the viral/immune trigger has been eliminated. In order to develop this as a model of CFS, in our three-year project we want to: 1) assess a cohort (n=100) of patients throughout the IFN-alpha treatment and at 6 months after cessation of treatment, and identify the group who develop the persistent post-treatment fatigue (expected n=50); 2) validate this model, by comparing the clinical and biomarkers profiles in patients who experience persistent post-treatment fatigue, patients with CFS (n=50), and healthy controls (n=50); 3) identify the risk factors and the biomarkers trajectories (before and during IFN-alpha treatment) that identify those patients who will later experience persistent post-treatment fatigue. We will measure: fatigue, mood, and other CFS-like symptoms; medical and psychiatric history; childhood and recent stressors; social support; illness and treatment perceptions; physical fitness; quality of life; and occupational function. Moreover, we will measure blood biomarkers: serum cytokines; cortisol at awakening and during the day; and leukocytes gene expression. The project will build onto an existing pilot study in HCV patients, an established collaboration with Liver Units across London, and the research-led clinical service for CFS patients at King's College Hospital. Thus, the project has great chances of success.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;6.1 PHARMACEUTICALS
Health categories: DISPUTED AETIOLOGY AND OTHER;INFECTION
Title: Sex and gene flow in the opportunistic fungal pathogen Aspergillus fumigatus.
Funder: Wellcome Trust

Abstract: The fungus Aspergillus fumigatus causes life-threatening infections in individuals whose immune system is not functioning correctly. Even with antifungal drug treatment the mortality rate can be as high as 50% or more. Aspergillus fumigatus can also cause asthma in otherwise healthy people. The fungus was thought to reproduce solely by producing microscopic spores, all identical to each other. But we have recently discovered that A. fumigatus from Ireland can reproduce sexually, involving two di fferent strains of the fungus coming together to produce new, genetically different offspring. If this can happen worldwide there is the danger that the species will evolve more rapidly to become resistant to antifungals and cause increased levels of disease. Therefore our research aims to determine if worldwide isolates of A. fumigatus can reproduce sexually, to provide an early warning for the medical community so that treatments are adapted accordingly. Conversely, we also want to see if we c an use sexual reproduction to better understand how the fungus becomes resistant to drugs and causes disease. By making sexual crosses and analysing the sexual offspring we aim to identify genetic factors responsible for drug resistance and disease, which will hopefully allow new methods of control to be devised.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: DISPUTED AETIOLOGY AND OTHER;INFECTION
Title: Phylogeography, Transmission Dynamics and Pathogenesis of Bluetongue.
Funder: Wellcome Trust

Abstract: Bluetongue is one of the most important diseases of livestock. The disease is caused by an arbovirus, bluetongue virus (BTV), transmitted by the biting midges. BTV is probably one of the best understood viruses with respect to its structure and replication. However, we have an incomplete understanding of the genetic variability of these viruses. This hampers efforts to determine the origin of some BTV outbreaks making it very difficult to quantify and minimise the risk of future ones. The common thread of this programme is that bluetongue and bluetongue virus are in reality a group of diseases induced by a variety of distinct viruses. BTV can induce a completely asymptomatic infection or kill the infected host. This variability is due to factors related to the virus, the host and the environment. We don t know what differentiate a highly virulent from a less virulent BTV strain. We have a limited understanding of the basis of the wide range of susceptibility to bluetongue displayed by different species and breeds of ruminants. In this ambitious programme, we will provide a multifaceted and holistic approach to understanding key aspects of BTV biology, transmission dynamics and pathogenesis.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: DISPUTED AETIOLOGY AND OTHER;INFECTION
Title: The phylogenetics and epidemiology of tuberculosis in cattle and their herders in Cameroon.
Funder: Wellcome Trust

Abstract: Bovine tuberculosis in an important infectious disease of livestock (particularly cattle), which, has the potential to infect humans exposed to infected milk or meat. This project will collect new data from a random sample of cattle across the three main cattle rearing regions of Cameroon (The North West, the Adamawa and the Extreme North) to identify management (herd-level) and animal-level factors that affect the spatial patterns of disease and which may identify mechanisms to improve control. Furthermore, screening of animals at slaughter will allow the identification of infected animals from which bacteria will be cultured and their specific genetic strain identified. Using the variation in these strains and linking it to management factors and animal movements, we will be able to understand the dynamic spread of the disease and potential critical control points in the production chain that would facilitate disease control. A crucial part of achieving this is having accurate and ea sy to use screening tests. The diagnostic test data will be analyzed using advanced statistical techniques which consider their interaction and the influence of co-infection to give maximum utility to their future application.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: DISPUTED AETIOLOGY AND OTHER;INFECTION
Title: Treatment support for older children and adolescents living with HIV: A household-randomised trial linked to evaluation of decentralised HIV testing and care in Harare, Zimbabwe.
Funder: Wellcome Trust

Abstract: Many infants infected with HIV at birth in the 1990s are now reaching adolescence. Most are undiagnosed and at risk of developing complications like lung damage and growth failure. Without support, children are less likely than adults to be able to come for check-ups or to take their treatment consistently, resulting in treatment not being effective. We will ask the following: 1. Can most older children be diagnosed by offering HIV testing to all children attending a primary care clinic (PH C)? 2. Are HIV-infected children likely to respond better to treatment if support is provided to the family? 3. Are children less likely to develop growth and lung problems if they are started on treatment even if their HIV is not at an advanced stage? We will offer HIV testing to any child who attends a PHC. HIV-positive children will be randomly selected for either HIV care at the PHC only or care at the PHC and treatment support at home by community workers. All children will have their lung function and growth assessed to study if those not taking HIV treatment (on the basis of their HIV infection not being at an advanced stage) are still at risk of developing lung and growth problems


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: DISPUTED AETIOLOGY AND OTHER;INFECTION
Title: How does the pathogen Candida albicans sense heat and activate the thermal adaptation mechanisms that promote infection?.
Funder: Wellcome Trust

Abstract: Candida albicans remains one of the most persistent yeast pathogens known to man. Candida frequently causes mucosal infections, such as oral and vaginal thrush. It also causes potentially fatal infections of the bloodstream and internal organs in cancer and transplant patients. Over 40% of these infections are fatal in some patient groups. To cause infections, Candida must be able to adapt to temperature fluctuations. Furthermore these temperature fluctuations affect key processes in Candida that promote the virulence of this pathogen. This is highly relevant because temperature fluctuations occur, for example, in patients with fevers. However, the molecular mechanisms by which Candida senses and adapts to thermal fluctuations, and how this is linked to virulence remain obscure. Therefore, my aims are to establish the nature of the thermal sensor in Candida, identify the thermostat that modulates the extent of adaptation based on the magnitude of the temperature change, and dete rmine how key molecular processes combine to mediate thermal adaptation. In addition I will determine the extent to which these mechanisms are evolutionarily conserved in a second major fungal pathogen of humans, Cryptococcus neoformans, and how these thermal adaptation components enhance the virulence of fungal pathogens.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: DISPUTED AETIOLOGY AND OTHER;INFECTION
Title: Leptospirosis in Tanzania: the role of rodents and cattle in a neglected public health problem.
Funder: Wellcome Trust

Abstract: In East Africa, fever is the most common reason for hospital attendance. Treatment has often been based on the assumption that most of these patients have malaria, but recent studies in Tanzania indicate that other infections, including those carried by animals (zoonoses) are more important than realised. Leptospirosis, a serious bacterial zoonosis, has been diagnosed in 9% of febrile patients admitted to hospital in Tanzania. Questions still remain about this infection which can be spread throu gh contact with urine from an infected animal or through contaminated food and water. This project aims to investigate how animal infection patterns are related to human disease risk by studying leptospirosis in rodents and cattle in an area of Tanzania where human disease is also being closely monitored. We will use new diagnostic tools to improve detection of leptospirosis in humans, and also use these tests to determine infection patterns in rodents and cattle in local communities. We will d etermine whether the same strain of leptospirosis affects both people and animals and conduct surveys to identify household and farming factors associated with infection. The results from the study will assist in developing strategies for the effective management, prevention and control of human disease.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: DISPUTED AETIOLOGY AND OTHER;INFECTION
Title: Natural history and pathogenesis of systemic IgG4 disease.
Funder: Wellcome Trust

Abstract: IgG4 systemic disease is a disease that can affect many organs and may mimic cancer. IgG4 is a specific type of antibody that is found in all people, and is a normal part of the immune system, made by a specific subset of circulating white cells called B cells. In the disease, B cells making IgG4 infiltrate different organs in the body, such as the pancreas and liver, causing them to malfunction. A collection of these infiltrates can mimic cancer. In some people, IgG4 disease is associated wit h elevated levels of IgG4 in the blood. However, not everybody with high levels of IgG4 develops IgG4 disease. We do not know what causes this disease or how it progresses. We do not have a reliable test or definitive treatment for all patients. And we do not understand what is so special about IgG4 and the cells that make it. This study aims to study a group of people we have carefully identified with IgG4 disease. We aim to assess the immune response to further understand why cells are making IgG4 and what role this plays in the disease process. Ultimately, this may help to develop a diagnostic test and better treatment.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: DISPUTED AETIOLOGY AND OTHER;METABOLIC AND ENDOCRINE
Title: Investigating adaptive immune function in ME/CFS patients
Funder: Wellcome Trust

Abstract: The underlying cause and the mechanisms driving disease in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) are unknown and identifying a marker of disease, even for a subgroup of patients, would open avenues for research into pathogenesis and better diagnostic tools. B cells in ME/CFS patients have been shown to have unusual features, including an expansion of particular B cell repertoires (BCRs) in the repertoires of a small cohort of ME/CFS patients compared with healthy controls [9]. We will test these initial findings across a large number of patients and examine patterns of diversity or shared responses in the repertoires of patients compared with controls. This will involve sequencing and analysis of B cell samples for approximately 130 severe and moderate ME/CFS patients as well as multiple sclerosis patients and healthy controls. Using machine learning and clustering-based statistical techniques we will stratify individuals based on properties of their B cell repertoires and the available meta-data. Phage display techniques will be used to replicate BCRs in the lab to identify major antigens shaping the repertoires in these patients. This study will generate a comprehensive picture of B cell immune diversity in ME/CFS to improve our understanding of the aetiology and immunopathology of ME/CFS.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: DISPUTED AETIOLOGY AND OTHER;NEUROLOGICAL;INFLAMMATORY AND IMMUNE SYSTEM
Title: Development of TIPS Microspheres for the Treatment of Fistulas.
Funder: Wellcome Trust

Abstract: Perianal fistulas are a connection between the anal canal and the skin surface creating an abnormal passageway for the discharge of bodily fluids. The goals of fistula treatment are to close the fistula after removing material from within that that might cause infection, whilst trying to avoid damage to the surrounding tissue that could cause incontinence. A range of materials have been used to fill fistulas in an attempt to promote healing but many of these have failed because the Science 7 material becomes dislodged and falls out or results in an infection. The use of highly porous microspheres might overcome this problem. When packed into a fistula the microspheres should provide a scaffold' that cells can easily grow between and into. As the microspheres slowly dissolve they are replaced by new tissue. The aim of this study is to demonstrate that properties of our experimental microspheres can be retained during manufacturing conditions necessary for use in humans and that the microspheres are safe when implanted into perianal fistulas in humans.


Research activity codes: 5.3 MEDICAL DEVICES
Health categories: DISPUTED AETIOLOGY AND OTHER;ORAL AND GASTROINTESTINAL
Title: From potential donor to actual donation: how does socio-economic deprivation affect the recruitment and progression of living kidney donors? A quantitative-qualitative mixed-methods observational study.
Funder: Department of Health (England)

Abstract: Socio-economically deprived people in the UK are more likely to develop kidney failure but less likely to receive a living-donor kidney transplant. Using a multi-centre mixed-methods study we will assess if deprivation affects potential donor recruitment and progression to surgery. The majority of those volunteering for donor assessment never actually donate: we ask if the reasons for this vary with deprivation. Semi-structured interviews will explore what makes a potential donor ‘unsuitable’ in an intended recipient's eyes. The findings of this observational project will be used to design a future intervention study, aimed at increasing living kidney transplantation for deprived patients.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: DISPUTED AETIOLOGY AND OTHER;RENAL AND UROGENITAL
Title: Connective tissue growth factor (CTGF) is a critical mediator of cryoglobulinaemia and kidney disease
Funder: The Dunhill Medical Trust

Abstract: Connective Tissue Growth Factor (CTGF) is a secreted matricellular protein, produced by different cells and involved in diverse cell functions. Since it was implicated in the development of diabetic kidney disease we developed a CTGF-over-expressing mouse, to investigate whether it would develop diabetic nephropathy. Much to our surprise, we found the mice did not develop diabetic changes rather they developed cryoglobulins and cryoglobulinaemic glomerulonephritis. We have confirmed that bone marrow from these mice can transfer disease suggesting that haemopoeitic cell CTGF overexpression is critical. Additionally we have demonstrated that cryoglobulinaemic patients have elevated serum CTGF levels and a second established model of cryoglobulinaemia, in TSLP-transgenic mice, also have elevated serum and thymic CTGF levels. Our serendipitous findings suggest a critical role for CTGF in B lymphocyte biology and in mediating cryoglobulinaemia, a common complication found in hepatitis C infected patients. We now wish to confirm and extend these findings.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: DISPUTED AETIOLOGY AND OTHER;RENAL AND UROGENITAL
Title: Bioethical decision making in the clinical practice of assisted reproductive techniques in non-human mammals.
Funder: Wellcome Trust

Abstract: Animal breeding has become increasingly high-tech, so that we have moved from a situation where natural cover was the norm to a situation in which assisted reproductive techniques (ARTs), particularly artificial insemination but also in-vitro fertilisation, embryo transfer, semen and embryo freezing and cloning, are practical techniques, with some being very common. The regulationof ARTs in veterinary science is under-developed when compared to their regulation in human medicine, and consequently what it is and isn't reasonableto do is largely the decision of the individual Vet. This research is divided into three studies: (i) Why the law is different for humans and for non-human mammals (ii) What the philosophical and ethical implications of legal differences are and (iii) The development of guidelines for use in clinical practice and suggestion of a technique for ethical clinical decision making inveterinary reproductive practice. Key goals are (i) Initiation of and contribution to debate about what the legal and ethical issues relating to veterinary ARTs are (ii) The establishment of a recognised and appropriate technique for ethical decision making in relation to clinical veterinary ARTs and (iii) dissemination of the research to policy-makers, regulators, monitors, clinicians and interested members of the public.


Research activity codes: 8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: DISPUTED AETIOLOGY AND OTHER;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Clinical proof of concept trial of a Kv3 modulator for the treatment of tinnitus
Funder: Innovate UK

Abstract: Tinnitus is a chronic, under-recognised condition that affects over 10% of adults, causing significant suffering. There are no approved drugs and current treatments, such as counselling, only help patients to cope with symptoms This project will provide clinical proof-of-concept evaluation of the efficacy of a novel ion channel drug in patients with tinnitus. AUT00063, currently completing Phase I trials, is being developed by Autifony Therapeutics for the treatment of age-related hearing loss; however, there is a strong scientific rationale to suggest potential for the drug to help control tinnitus. Autifony will work in collaboration with leading tinnitus expert, Prof Deborah Hall, Director and Research lead for Tinnitus aetiology and management at the National Institute for Health Research, Nottingham Hearing Biomedical Research Unit, University of Nottingham, on this clinical trial as a major step towards potentially the first effective oral drug to treat tinnitus.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: EAR
Title: Audiological characteristics and mitochondrial function in patients with m.1555A>G mitochondrial mutation
Funder: SPARKS

Abstract: We aim to investigate biochemical and clinical differences in people with a genetic mutation called m.1555A>G, that predisposes them to antibiotic associated hearing loss and age-related hearing loss. We will see if there are differences in m.1555A>G cell lines between those with normal hearing, those who have hearing loss without exposure to aminoglycosides (age-matched), and normal controls by:Testing and developing assays of mitochondrial function/dysfunction in cell lines, Choosing a method for scale-up to high-throughput analysis of drugs including whether artificial cell-free mitochondrial translation systems (mutant and normal) can be adapted for high-throughput


Research activity codes: 5.1 PHARMACEUTICALS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: EAR