NIHRDataInsights/HRCSData huggingface dataset:
Title: Doctoral Fellowship - Jonathan Fee - Improving Primary Care Assessment of Skin Disease through an Examination of the Use of Patient-Acquired Photography by General Practitioners
Funder: Public Health Agency, NI

Abstract: Skin assessment forms a very large part of general practitioners’ (GPs’) work. It is primarily a visual skill, usually requiring a patient to have a face-to-face assessment. However Covid-19 has transformed GP consultations, with practices now operating a ‘telephone first’ approach, whereby patients speak with a GP by telephone and send photographs into the surgery if needed. Only thereafter, if necessary, are patients offered a face-to-face appointment. Many GP practices plan to continue consulting like this in the longer-term. However, this new system of combining telephone calls with patient-acquired photography to assess skin complaints has been implemented without an empirical evidence base or relevant guidelines. Understanding whether patient-acquired photography is a satisfactory, effective or costeffective mode of assessing skin complaints is essential for its continued use to be justified.This proposal aims to develop a model patient-acquired photography intervention for the assessment of skin complaints by GPs; and to test the feasibility of a randomised trial to determine whether GP consultations of patients’ skin complaints using patient-acquired photography are as effective and cost-effective as face-to-face consultations. A rapid review looking at the use of patient-acquired photography for the assessment of skin complaints will be carried out, together with a review of guidelines on the use of mobile photographic devices in clinical assessment. Qualitative methodologies will be used to investigate patients’ and GPs’ perceptions on the use of patient-acquired photography for skin assessments. This evidence will inform the development of a model patient-aquired photography intervention. A feasibility study will explore whether patients presenting to GPs with skin complaints can be recruited to and randomised in a trial to compare the effectiveness and cost-effectiveness of GP consultations using patient-acquired photography with face-to-face consultations. Research findings will inform the use and conduct of consultations using patient-acquired photography and underpin a future trial to test the effectiveness and cost-effectiveness of patient-acquired photography for the assessment of skin complaints in primary care.


Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING
Health categories: SKIN
Title: Electrical stimulation for chronic diabetic ulcers healing
Funder: Wellcome Trust

Abstract: Wound healing is a complex process wherein the tissue undergoes inflammation, repair and maturation to re-establish initial equilibrium. When transition between the stages fails, the tissue remains stuck in an inflammatory state, deferring healing and greatly increasing the probability of systemic infection, which may lead to member amputation or even death. Chronic wounds are prevalent in diabetic patients and represent an individual as well as a societal financial burden. Despite of this, it is still unclear how to robustly regulate the process to exit the chronic state and few advanced therapies show evidence of improving the outcome compared to standard treatment. Electric stimulation (ES) is a promising non-invasive procedure that was shown to influence the behaviour of the cells leading the immune and repair response to skin damage. ES was shown to modulate exchange of calcium whose changes in level are correlated with wound stages. The project aim is to define effective time dependent ES regimes that promote the healing of diabetic ulcers by characterizing normal and diabetic-derived cells and their response to ES. Furthermore, calcium signalling will be investigated to reveal ES mechanisms driving cellular response.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: SKIN
Title: Assessing the printability of nanocellulose composite bioinks for 3D printing facial cartilage
Funder: The Scar Free Foundation

Abstract: This research aimed to develop a novel, natural nanocellulose bioink with ideal properties for three[1]dimensional (3D) bio-printing. This bioink was developed with a view to producing tissue-engineered constructs for use in reconstructive facial surgery. Extrusion-based 3D bioprinting is a tool in the field of tissue engineering, that combines material science, 3D printing technology and regenerative medicine. Natural polymers such as alginate (Alg), plant-derived nanocellulose (NC) and hyaluronic acid (HA) offer excellent characteristics for use as bioinks due to their biocompatibility and printability. In addition to this, Tunicate nanocellulose (TC) is an exciting new alternative which has clear advantages over wood-based nanocellulose blends (NCB) due to its very high purity and crystallinity index but is relatively underexplored in the context of tissue engineering. We determined the printability of new bioinks using three structurally different TC variants, and their behaviour post-printing both with and without crosslinking. Additionally, we determined the optimal crosslinking time for alginate-nanocellulose composite bioinks, followed by an assessment of the post-printing shape fidelity. Results showed that the optimal crosslinking time was 10 minutes and post-printing shape fidelity showed two of the three TC variants reduced in size following crosslinking, forming a stiff and stable structure. This promising initial data highlights a potential role for tunicate nanocellulose bioinks in tissue engineering cartilage for facial reconstruction, in particular when combined with alginate and HA. This type of work will contribute to revolutionising the way we reconstruct form and function, whilst negating the complications that accompany tissue grafting.

Lay abstract: The study incorporated the following research objectives: To produce bioinks containing mixtures of nanocellulose, hyaluronic acid and alginate; To determine the minimum and optimum printing pressures of the composite bioinks; To perform printability assays to determine filament strength, printing resolution and post-printing shape fidelity of the bioink formulations; To determine whether relevant anatomical structures can be produced using the bioinks and to determine their accuracy to the intended designs.

Research activity codes: 1.3 CHEMICAL AND PHYSICAL SCIENCES;5.4 SURGERY
Health categories: SKIN
Title: A prospective randomised controlled trial to examine the efficacy and mechanistic basis of fractional ablative carbon dioxide laser therapy in treating hypertrophic scarring (SMOOTH)
Funder: The Scar Free Foundation

Abstract: Photo-thermal therapy (laser therapy) is one of the newer treatments developed to reduce established hypertrophic scars. Despite its broad usage its efficacy has not been definitively established due to suboptimal randomised control trial (RCT)design, varying patient selection, including the use of different laser types and a wide variety of outcome measures. In addition, exactly how laser works to reduce scars is poorly understood, further limiting optimisation and patient stratification. This pilot study on two sites aims to develop a robust protocol to assess efficacy of laser, considering feasibility of recruitment, retention in the study and suitable outcome measures using a fractionated laser therapy. The study aims to recruit 60 patients with established hypertrophic scars, from both military and civilian patients and will apply laser therapy to half of a scarred tissue area and leave the other half untreated. Patients will therefore act as their own controls. Assessment of scarring will be carried out blinded, using a range of patient derived and clinician derived outcome measures by 3 independent assessors. In this way we will be able to move forward to a larger RCT of sufficient size and scope to look at laser therapy efficacy, patient factors influencing outcomes such as gender, skin type and age, with sufficient data to develop a robust protocol and gain funding from a source such as NIHR. Additionally, the study will take biopsy samples across the treatment period to determine the cellular and molecular features of the response to laser therapy and associate these with the degree of scar reduction. These data will identify the tissue-based mechanisms driving a good response to laser therapy and may help to identify further modifications or adjunct therapies to improve treatment efficacy.

Lay abstract: In this clinical trial, which involves civilians and military veterans with scars that are over a year old recruited from Burns Centres in Birmingham and Swansea, we are assessing the effectiveness of laser therapy to breakdown scar tissue from burn and blast injuries and restore lost function

Research activity codes: 6.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: SKIN
Title: Skin safety testing to enable far-UV-C technologies for wide-spread inactivation of SARS-CoV-2
Funder: Innovate UK

Abstract: UV light is known to inactivate SARS-CoV-2, the virus responsible for the COVID-19 pandemic. It is also widely claimed that high energy UV light, called "far-UV-C", is 'safe for humans', although this claim is based predominantly on animal studies and limited studies in human volunteers. The UK is expected to begin employing far-UV-C in public spaces in 2021\. It is proposed here to _rapidly_ generate safety data showing whether or not far-UV-C causes the types of damage that full-spectrum UV light does (for example, sunburn, DNA damage, immunosuppression of the skin, and modifications to the skin microbiome, which is the natural flora that lives in healthy human skin). It is imperative that we understand the effects of far-UV-C on human skin to ensure it can be deployed to its full effect We are proposing here to conduct the following far-UV-C research projects to investigate the efficacy and safety profile of this very promising technology: * DNA damage upon acute and chronic far-UV-C exposure * DNA damage to compromised skin (for example, wounded skin) upon far-UV-C exposure * Response of immune cells resident in the skin to far-UV-C (it is known that UV-B light elicits an immune response in skin, but the effect of far-UV-C has not been evaluated) * Evaluation of skin microbiome following acute and chronic exposure to far-UV-C. Far-UV-C irradiation may kill or modify the genetic material of the beneficial flora that colonise the skin by the same mechanism by which SARS-CoV-2 is inactivated * Computer simulation of far-UV-C penetration into skin guided by the data generated in the skin model We propose to conduct these experiments in our novel patent-protected _ex vivo_ skin model (TenSkin(tm)) which is the closest mimic available to human skin while still on the body.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: SKIN
Title: Journeys of hair-loss. An exploration of men’s experiences of pattern baldness
Funder: The British Academy

Abstract: The experience of going bald can be a turbulent and, sometimes, distressing life transition for men, with implications for wellbeing, identity and everyday life. Yet detailed, contextualised knowledge of how different men respond, adapt and cope with the process of such a significant change to their appearance is surprisingly scarce. This exploratory research project on male androgenic alopecia, or pattern baldness, offers a much-needed in-depth examination of the journeys men go through as they lose hair, with a particular emphasis on the individual and social challenges they face, and developing approaches to accepting, resisting or adapting to hair-loss. Taking a biographical approach centred on the development of experiences, understandings and modes of adaption over time, the research will capture rich accounts from forty men to provide much-needed knowledge and recommendations on men’s experiences of hereditary hair-loss and how they could be eased.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: SKIN
Title: Role of MicroRNA-7 in the Age-Related Impairment of TGF-1-driven Differentiation in Chronic Wound Fibroblasts
Funder: Division for Social Care and Health Research (Wales)

Abstract: Chronic wounds, such as venous leg ulcers and diabetic foot ulcers, occur in around 3% of the Welsh population and cost NHS Wales upwards of £30 million per year to treat. These wounds are becoming a significant problem to healthcare providers, especially with the increasingly ageing population within Wales and beyond. Described as skin wounds that fail to heal, these represent a major cause of disability and distress, especially amongst the aged. In chronic wounds, we know that the fibroblast cells responsible for repairing these wounds do not perform their healing functions as effectively as they should, partly as chronic wound fibroblasts appear much ‘older’ than fibroblasts from normal skin. We have been examining what causes ‘older’ fibroblast cells to behave differently to ‘younger’ fibroblasts in normal skin, to help us understand why chronic wounds fail to heal. Recently, we have identified a new important molecule in ‘older’ fibroblasts, called microRNA-7 (miR-7), which prevents these cells from being able to heal wounds. In this study, we wish to examine the effects of miR-7 in fibroblast cells collected from patients with venous leg ulcers and normal skin, in order to further understand what role miR-7 has in preventing these chronic wounds from healing. We already have fibroblast cells from venous leg ulcers and normal skin available, which we have collected during previous studies. The ability of miR-7 overproduction to prevent normal wound healing in fibroblast cells from chronic wounds will be determined utilising established laboratory-based techniques. By identifying how miR-7 prevents chronic wound healing, we can then begin to develop new treatments in future to counteract the effects of miR-7 so allowing chronic wounds to heal normally, thereby improving the quality of life for the increasing ageing population within Wales and beyond.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: SKIN
Title: The role of CD1a-restricted T cells in the pathogenesis of atopic eczema
Funder: Medical Research Council

Abstract: Atopic eczema (AE) affects 20-30% of the UK population. Both genetic and environmental factors interact to contribute to pathogenesis, with convincing evidence of both a compromise in epidermal permeability through null mutations in the filaggrin gene and a Th2 driven cutaneous inflammatory response. There is significant complexity in regulation of the skin barrier, and mechanisms by which filaggrin insufficiency leads to atopic disease are poorly understood. In recent years, T cells recognising lipids in the context of CD1 molecules have been described, with evidence that CD1a-restricted T-cells (CRTC) circulate at higher frequencies than previously considered and can infiltrate human skin. CD1a is highly expressed by epidermal Langerhans cells which are well placed to detect barrier compromise, lesional atopic tissue carries an altered lipid profile, and CD1a+ cells are enriched within AE lesions. I therefore propose that epidermal CD1a-restricted T cells contribute to atopic inflammation and wish to test the hypothesis that AE is associated with an altered frequency and phenotype of CRTC by addressing the following questions in individuals with AE and non-atopic controls: 1.) What is the frequency and phenotype of CRTC in the blood and skin of atopic and control individuals with defined filaggrin genotypes? 2.) How do cytokines derived from cutaneous CRTC influence keratinocyte biology? 3.) Are CD1a-restricted T cells in atopic individuals reactive to common environmental allergens? Through these approaches I will identify how CRTC cytokines contribute to a milieu linking filaggrin insufficiency, CD1a+ cells, and T cells in the pathogenesis of AE.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: SKIN
Title: The Genetic Epidemiology of Atopic Dermatitis
Funder: Medical Research Council

Abstract: A comprehensive program of genetic epidemiological analysis for atopic dermatitis (AD), using state-of-the-art technologies & analytical methods. Objectives: 1 Refine the AD phenotype definition using latent class analysis in a longitudinal epidemiological study, incorporating various data from multiple time points 2 Quantify the overall contribution made by common genetic variants to AD susceptibility & identify important pathways 3 Carry out a large-scale genome-wide association meta-analysis of improved AD definitions & subtypes 4 Refine existing signals and investigate the role of lower frequency variants in AD using next-generation sequencing 5 Investigate parent-of-origin effects using multi-generational data 6 Investigate 'gene-gene' & 'gene-environment' interactions for AD 7 Functional follow-up of AD associated variants using methylation and expression data. Main dataset:The Avon Longitudinal Study of Parents And Children. Extensive phenotypic data has been frequently collected via clinics & questionnaires. Mothers & children have imputed genome-wide SNP data & next-generation sequencing (NGS) data will soon be available for the children. Expression and methylation data will also be available. Additional datasets:Through existing and planned collaborations in the EAGLE consortium, I will have access to a unique resource of datasets, including TwinsUK (with NGS data), the GOYA cohort (with multi-generational data) and two family-based cohorts at QIMR. Methods:Latent class analysis to investigate the phenotype, whole-genome methods for exploring the common genetic contribution to AD, genome-wide association analysis and meta-analysis to identify associated common variants and interactions, and collapsing techniques for identifying lower frequency variants from NGS data. This work will increase the molecular understanding of the development of AD. This will in turn enable future treatments for AD to be designed.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: SKIN
Title: Investigating Rhomboid Regulation of ADAM17 in Psoriasis and Skin Biology
Funder: Medical Research Council

Abstract: Background: Psoriasis is a common inflammatory disease. TNFa is thought to play an important role in its development. ADAM17 is a membrane bound-metalloproteinase whose "sheddase" activity includes the release of soluble TNFa. We hypothesise that the rhomboid protein iRHOM2 plays a role in regulating ADAM17. Aims and Objectives:1.Examine the effect of mutated iRHOM2 on ADAM17 expression and inflammatory cytokines. 2.Localisation and expression of iRHOM2 and ADAM17 in psoriatic skin and effect of TNFa blockade 3.The effect of broad-spectrum ADAM inhbitors on keratinocyte behavior and cytokine expression. Methods:1.Keratinocytes derived from patients with mutant iRHOM2 ("Tylosis with Oesophageal Cancer") will be used to form organotypic models, characterized with a panel of proliferation and expression markers including ADAM17 and TNFa. The effects of "knock-down" of iRHOM2 will be assessed. 2.Skin biopsy specimens taken from untreated psoriasis and repeated after initiation of anti-TNFa drugs and will be stained for ADAM17 and iRHOM2 using immunohistochemistry. RTQ-PCR will be used to assess expression of ADAM17 and iRHOM2. siRNA mediated knockdown of iRHOM2 in immortalized psoriatic cell lines will be performed to study the effects on ADAM17, TNFa, TGFa and EGF expression.3.Broad spectrum ADAM inhibitors will be applied to cultured cells from psoriatic and tylosis lines, to assess the impact on cell behavior, proliferation rates and "scratch assays". Immunohistochemistry and confocal microscopy will be used to determine localisation of iRHOM2 and ADAM17. Scientific opportunities: I will learn cell and molecular biology skills including monolayer and complex cell culture, siRNA, western blotting, RT Q-PCR, immunohistochemistry and confocal microscopy. Medical opportunities: Understanding the regulation of ADAM17 could identify novel targetable pathways for the treatment of psoriasis and other inflammatory diseases and malignancies in which TNFa plays a central role.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: SKIN
Title: Role of microRNA-214 in the control of skin regeneration
Funder: Medical Research Council

Abstract: Skin development and regeneration are governed by complex programmes of gene expression activation and silencing. Recent data demonstrate that activity of many genes implicated in the control of skin homeostasis is regulated by miRNAs, which represent a new regulatory layer during execution of tissue-specific differentiation programmes. This project will investigate the role of miR-214 in the control of stem cells and their lineage-committed progenies during skin postnatal regeneration and wound healing. Our preliminary work has demonstrated the role of miR-214 in regulating the activity of the Wnt/beta-catenin signalling pathway in keratinocytes and showed that doxycycline-inducible miR-214 (K14-rtTA/TRE-miR-214) transgenic mice develop a skin phenotype (markedly decreased number of hair follicles and delayed onset of hair follicle growth phase) that strikingly resembles the phenotype of beta-catenin knockout mice. We will test the hypothesis that miR-214 is involved in the control of skin regeneration by regulating the activity of Wnt signalling and cell cycle-associated machinery in epithelial stem cells and their lineage-committed progenies. This hypothesis will be addressed via two specific aims: 1) to define how modulation of miR-214 levels affects proliferation, differentiation and gene expression programmes in epithelial stem cells and their lineage-committed progenies during skin development and physiological regeneration; 2) to delineate the role of miR-214 in the control of injury-associated gene expression programmes in epithelial stem cells and their progenies during wound healing. Outputs from this project will provide new important insights into fundamental mechanisms that regulate stem cell activity and cell fate decision inside and outside of the skin, and will be highly important for the development of novel miRNA-based approaches for rapidly developing areas of regenerative medicine and stem cell-based therapy.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: SKIN