NIHRDataInsights/HRCSData huggingface dataset:
Title: Understanding the Role of Adolescent Dysmenorrhoea as a risk factor for the transition to chronic Pain (RoAdPain)
Funder: Medical Research Council

Abstract: Chronic pain affects up to 30% of people worldwide with significantly reduced quality of life and associated socioeconomic cost. Once established it is difficult to treat and therefore preventative strategies are urgently required. Being a woman is a risk factor for chronic pain and this sex difference emerges after puberty. Periods, which start during puberty, are themselves painful for many women. Alterations in a variety of pain-relevant body systems have been demonstrated in adults with dysmenorrhoea, including sensitivity to noxious stimuli, visceral sensitivity, brain structure and function and activity of both the hypothalamic-pituitary-adrenal axis and the autonomic nervous system. We hypothesise that the experience of dysmenorrhoea during adolescence is a risk factor for the development of chronic pain, with the potential to act through a variety of pathways. We will address this in two ways. Epidemiological analyses will use the ALSPAC data, a resource that has been collecting prospective data from children born in the early 1990s and their parents for almost 30 years, to determine whether adolescent dysmenorrhoea is an independent risk factor for chronic pain in young women. We will additionally explore whether factors present in childhood increase the risk of dysmenorrhoea early in menstrual life. Alongside this work, an experimental study using psychophysical and neuroimaging assessments will determine whether dysfunction in pain-relevant systems can be demonstrated in adolescent girls in the early years of menstruation. We anticipate results with clear and direct implications for adolescent menstrual health and for drug target discovery of relevance to chronic pain in women. We will use findings from this project to highlight the importance of dysmenorrhoea and optimise its timely management. Ultimately we hope that this work will reduce the risk of both adolescent girls and adult women suffering with dysmenorrhoea and other chronic pain conditions.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: GENERIC HEALTH RELEVANCE;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Engaging Roma women in the co-design of an antenatal care information resource (ERicar)
Funder: Medical Research Council

Abstract: Our research employs a person- and community-centred participatory research approach that harnesses the potential of Roma women to develop tailored resources to meet their antenatal care information needs, through two reviews and design-based participatory activities. Work package 1: a scoping review of relevant literature referring to Roma women's experience of healthcare in Europe (2010-2022) for background information a review of publicly accessible antenatal information, examined and evaluated for the quality of their content and presentation using content analysis. Work package 2: Up to eight participatory workshops over five months, with 8-10 Czech-Slovak Roma women purposively sampled (i.e., age, parity), employing design-based methods e.g., mind-mapping and storyboarding, to capture the 'pregnancy stories' of the participants. Women will discuss access and experiences of healthcare, for e.g., cultural beliefs about pregnancy and childbirth, language support, home remedies, diet and exercise, and pregnancy-related health problems. The different information resources selected from the review will then be presented to the women to consider. The last two workshops will aim to co-produce a summary of the findings and a co-created prototype for a subsequent development. Participant observation will record and produce a descriptive model of the process as part of the evidence pathway. Researchers will agree a coding frame after independently coding samples of recorded data, meeting monthly with the expert advisory panel to reflect on the research process. Data will be analysed thematically with the help of NVIVO software. A stakeholder engagement workshop will present the following results: i) an understanding of Roma women's healthcare experiences and antenatal care information needs, ii) their assessment of publicly available antenatal care information resources and iii) a low-resolution prototype of a resource reflecting women's preferences.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: GENERIC HEALTH RELEVANCE;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Embryo architecture, potency and tissue interactions during mouse and human development
Funder: Wellcome Trust

Abstract: Mammalian embryogenesis entails close partnership between embryonic and extra-embryonic tissues to regulate changes in embryo architecture and developmental potency. We aim for an integrated view of how these events progress hand in hand during key stages of mouse and human embryogenesis. The first architectural changes of the embryo are polarisation and compaction that trigger the separation of embryonic and extra-embryonic lineages. Yet their own trigger remains unknown. We will dissect potential triggering pathways and through genetic manipulations determine their importance for cell fate. Embryo remodelling at implantation is intimately associated with pluripotent-state transitions. We will harness our novel techniques for embryo culture throughout implantation to uncover mechanisms behind these events in relation to signalling partnerships between embryonic and extra-embryonic tissues. By arranging partnership between embryonic and extra-embryonic stem cells in 3D-culture we have recapitulated embryo-like morphogenesis and spatio-temporal gene-expression. We will characterise tissue interactions in such stem cell-derived embryos to understand principles of self-organisation. Our work established an unprecedented opportunity to study human early post-implantation embryogenesis in-vitro. We will build the first morphological and transcriptional atlas of human development beyond implantation. This will bring understanding of normal development and shed light upon why many pregnancies fail at early stages.

Lay abstract: The first weeks of embryo development from a fertilised zygote is a critical period when many pregnancies fail. To understand these developmental stages we aim to relate how changes in embryo architecture go hand in hand with new genetic instructions to give the early embryo its correct anatomy. We will begin our studies when the embryo comprises only eight cells and first changes its shape, important for different cell types to emerge. The embryo next changes its architecture when it implants into the womb and becomes inaccessible. To overcome this difficulty, we have developed technology for culturing mouse and human embryos in a dish throughout and beyond implantation (under approved conditions). This will now allow us to uncover mechanisms underlying the remarkable self-organisational properties of the mammalian embryo. In addition, we have established conditions in which stem cells in a dish develop into structures strongly resembling natural embryos. Using these novel insights, we will study previously hidden stages of our own development to understand how the different cell types interact to shape the body plan. These interactions are prerequisites for successful pregnancy and thus the basic knowledge we will acquire, will provide insight into the causes of early pregnancy loss.

Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: GENERIC HEALTH RELEVANCE;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Scaling up effective interventions to reduce maternal hypertensive disorder and gestational diabetes: A return on investment case for Bangladesh
Funder: Wellcome Trust

Abstract: Every year over 130 million children are born around the world. Each year 303,000 mothers die in childbirth while over 2 million children die at birth. Ninety nine percent of these deaths take place in low and middle income countries. In Bangladesh, the mother dies in 196 per 100,000 births per year. There is growing interest in the effect of non-Communicable Diseases(NCDs) on maternal deaths. Almost 14% of deaths are due to high blood pressure during pregnancy and 28% are due to other causes including diabetes. One in 25 women develop diabetes during pregnancy period. Addressing these two conditions can help prevent serious birth outcomes like the death of the baby or mother. Preventing high blood pressure and diabetes during pregnancy will also reduce the risk of development of other health problems among women and their children. I aim to conduct research focusing on addressing these two conditions in the context of Bangladesh. I will identify a number of interventions to be included within the public health services. In doing so, I will review evidence to understand current practices and analyse data in order to identify the best interventions in terms of saving lives, reducing ill-health and saving costs.


Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING
Health categories: GENERIC HEALTH RELEVANCE;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: The use of machine learning techniques to assess the quality of mammalian pre-implantation embryos
Funder: Wellcome Trust

Abstract: The popularity of in vitro fertilisation (IVF) is growing with techniques improving over the last few decades. Nevertheless, current success rates remain low, which is partly due to difficulty in selecting the best embryos to be used, as we lack a comprehensive understanding of the visual attributes of a healthy embryo. The aim of this PhD is to develop techniques that will improve the chances of selecting a healthy embryo after IVF procedures, based on a video of the first 5 days of its life. We plan to achieve this using machine learning, an artificial intelligence approach that allows computers to learn from available data. We will follow two approaches; 1) attempt to predict the quality of a human embryo using videos provided by an IVF clinic, and 2) create mouse embryos with abnormalities in genetic material, record their development and develop an algorithm capable of identifying the reasons behind developmental failure from image / video data. If we can correctly predict the viability of an embryo and genetic issues impacting on this, it will pave the way for the development of improved detection and diagnosis systems to support human IVF treatment.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: GENERIC HEALTH RELEVANCE;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: SUNRISE cluster RCT: Scaling Up Nurturing care, a Radio Intervention to Stimulate Early child development in Burkina Faso
Funder: Wellcome Trust

Abstract: The Nurturing Care Framework (NCF) launched by WHO, UNICEF and the World Bank during the 2018 World Health Assembly argued that “Investing in early child development (ECD) is one of the best investments a country can make to boost economic growth, promote peaceful and sustainable societies, and eliminate extreme poverty and inequality.” 250 million children under five in low and middle-income countries are at risk of not reaching their developmental potential with adverse consequences for their learning and adult prosperity. The NCF is a roadmap for action, focussing on pregnancy and the first 3 years of life as the foundation for wellbeing throughout the life-course. It includes interventions promoting responsive caregiving and early learning, known to improve ECD outcomes when delivered in face-to-face or group sessions with parents and children. However, doing this at the scale needed presents enormous challenges, as many health systems are over-stretched and under-resourced. Mass media may provide a more effective way forward. We plan to explore this by developing a nurturing care radio campaign built on principles of Saturation and Interactivity informed by clinical psychology, behavioural science and epidemiologic evidence, and to evaluate the impact on ECD outcomes using a cluster randomised trial design.

Lay abstract: Almost 250 million children under-five-years of age in low and middle income countries are at risk of not reaching their developmental potential. These children are more likely to do poorly in school, have lower incomes and poorer life chances. Between 0-3 years of age the brain develops quickly, and studies have shown that improving caregiver interactions and learning opportunities at this time can positively impact child development, with effects lasting into adulthood. Although impactful, these interventions can be labour intensive and delivering them within current health systems is challenging. We plan to test whether a mass media campaign can improve care-giving behaviours, learning opportunities and consequently child development in Burkina Faso. Unlike the current interventions mass media can deliver messages to millions of people several times per day. It has the potential to shift social norms and attitudes, model skills and create an enabling environment for behaviour change.

Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: GENERIC HEALTH RELEVANCE;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Equity & difference: Deconstructing gender in health research for women
Funder: Wellcome Trust

Abstract: Despite policy changes and advocacy efforts to promote the inclusion of women as participants in research and to advance a global agenda of women’s sexual reproductive health over the past two decades, women remain significantly underrepresented in biomedical research and its translational outputs beyond reproductive health. In this empirical ethics project, we will investigate the reasons why structural barriers to women’s health improvements persist within the practices of research itself—in how research is designed, conducted, and translated. More deeply, we will interrogate the role that implicit and explicit moral attitudes, beliefs and arguments play in making the case for a focus on women’s and girl’s health needs, and in the reactions to these priority-setting appeals in academic, policy, and social media domains. Taken together this work aims to make a significant contribution to evidence-based advocacy within biomedical research practice, transforming how researchers think and do research with and for women and girls.

Lay abstract: Scientists create knowledge through research, and biomedical researchers working in chronic disease and women’s health create knowledge that shapes how we think about the importance of women’s health and medical interventions for women. While moral beliefs and assumptions about women, their bodies, and symptoms, are often hidden within the way research is designed, carried out, and shared with the public, this research ethics project will seek to uncover ethical beliefs and potential gender biases in biomedical research through creative partnerships with scientists working in chronic disease, sexual reproductive health, maternal-newborn health and other research areas. Our goal is to inform critical debates around sex, gender, and research ethics that recognizes the important role that scientists play in advocating for under-represented groups in biomedical science—including women and girls. We hope our ethical arguments will inform a more equitable way of generating biomedical knowledge for everyone.

Research activity codes: 8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: GENERIC HEALTH RELEVANCE;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: The Future of Human Reproduction: transformative agendas and methods for the Humanities and Social Sciences
Funder: Wellcome Trust

Abstract: New and emerging reproductive technologies have the potential, within a generation or two, to profoundly disrupt established social practices linked to human reproduction and parenting, as well as the concepts of relatedness and family. Better understanding the cultural, ethical, legal, and social issues that this prospect raises is the principal substantive research aim of this programme. We will examine three such technologies. Ectogenesis could allow us to develop fetuses wholly outside the body, to create children who have not been ‘born’ (in the usual sense of that term). Genome editing will mean that future children can be ‘chosen’ or ‘designed’ with far greater levels of precision than at present. New methods of creating eggs and sperm will enable the creation of children with two genetic parents of the same sex, or who have multiple genetic parents, or perhaps no determinate genetic parents at all. Using these cases as focal points, we will develop transformative new research methods and modes of interdisciplinary working - for example, by integrating speculative design methodologies with those of bioethics, law, literature, linguistics, and psychology. Our ultimate aim is for this to lead to a novel research paradigm for the study of disruptive emerging technologies.

Lay abstract: Before the end of this century, the ways in which we create babies may alter dramatically. At present, the vast majority of children are created as a result of sexual intercourse, and subsequently pregnancy and childbirth. That may change however as science offers new options. These include: • pregnancy and childbirth being partly, or even completely, replaced by an ‘incubator’ for the developing fetus; • people being able to create eggs/sperm from bodily cells, like skin cells; • ‘genome editing’, which will enable us to select or deselect, to a much greater extent than we can now, the physical characteristics of our future children. These developments will raise a lot of difficult ethical, legal, and policy questions. This project seeks to help understand these by bringing together experts from very different fields including design, law, linguistics, literature, philosophy, and psychology. Ultimately, this should result in brand new ways of studying emerging technologies.

Research activity codes: 2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY);8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: GENERIC HEALTH RELEVANCE;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Cellular Dynamics and Regulatory Networks Controlling Endometrial Remodelling during the Window of Implantation
Funder: Wellcome Trust

Abstract: The endometrium undergoes iterative cycles of menstrual shedding, regeneration, rapid growth, and differentiation in response to ovarian hormones. During the mid-luteal phase, the endometrium becomes transiently receptive to implantation, heralding the start of a process of intense tissue remodelling, characterized by secretory transformation of glandular epithelium, angiogenesis, differentiation of stromal cells into secretory decidual cells, and activation of specialized immune cells. Several reproductive disorders, including recurrent pregnancy loss, are linked to defects in tissue remodelling at implantation. However, the cellular complexity and dynamic nature of the endometrium have so far precluded precise characterization of the underlying pathological mechanisms and drivers. We will employ high-throughput single-nucleus sequencing to map the dynamic changes in gene expression and chromatin accessibility (cis-regulatory regions) in all endometrial cell types across the luteal phase in defined patient groups. The data will be back-mapped to a future successful pregnancy or miscarriage. This analysis will yield unparalleled insight into the sequence of endometrial events (i.e. changes in cell populations, cellular states, gene expression and transcriptional regulation) leading to a successful or failed pregnancy. Further, 3D organoid cultures, consisting of glands and stroma, will be used to investigate putative drivers of endometrial dysfunction and to evaluate new treatment targets.

Lay abstract: Miscarriage is a profoundly devastating experience and for many couples the level of grief is similar to that of stillbirth. Chromosomal errors in the embryo often account for sporadic (occasional) miscarriage but persistent defects in the lining of the womb (endometrium) lead to recurrent pregnancy loss. Because the endometrium is such a dynamic tissue that changes day-by-day, it has been challenging to identify the pathways that cause recurrent pregnancy loss. Consequently, there are no effective interventions. Single-nucleus sequencing is a new technology that measures gene activation (expression) in thousands of individual cells in a single assay. We will use this technology to map normal and abnormal changes in gene expression in every endometrial cell type across the implantation window prior to a successful or failed pregnancy. By modelling specific defects in 3D endometrial cultures, this project will pinpoint the cause of recurrent pregnancy loss and identify new treatment targets.

Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: GENERIC HEALTH RELEVANCE;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Placental epigenetic programming: elucidating a role in cellular identity and transcriptional plasticity
Funder: Wellcome Trust

Abstract: Pregnancy complications affect as many as one in four pregnancies, yet there remains a critical gap in our knowledge of their underlying aetiologies. As the maternal-foetal interface, the placenta is essential for healthy pregnancy, with poor function being strongly associated with pregnancy complications. However, there is little mechanistic understanding of the molecular events regulating placental development. My research programme will investigate mechanisms of epigenetic programming and gene regulation in early placental trophoblast and reveal how these underpin the development of a functional placenta. Specifically, I will test the hypothesis that epigenetic programming in placental trophoblast is critical for (1) setting up the gene regulatory landscapes in placental cell types and (2) directing appropriate differentiation during placentation. I will apply cutting-edge ultra-low input sequencing methodologies to characterise gene expression, epigenetic marks, transcription factor binding and 3D chromatin folding in multipotent trophoblast cells in mouse embryos. Using single-cell sequencing and histopathology, placental genomic regulation and function will be evaluated in knockout mouse models for epigenetic modifiers, including several histone and DNA methyltransferases. This research will be fundamental to our understanding of placental development and provide novel insights into how errors in epigenetic programming can lead to compromised placental function in pregnancy.

Lay abstract: Pregnancy complications affect as many as one in four pregnancies, yet there remains a critical gap in our knowledge of the underlying causes. The placenta not only supports the growth of the baby in pregnancy, but helps the mother’s body adapt. A poorly functioning placenta is linked to pregnancy complications, but we have a poor understanding of early molecular events that direct healthy placental development. My research will characterise two early epigenetic events in placental cells and uncover how these are required for its development, using the mouse as a model. I will apply cutting-edge sequencing technologies to map epigenetic features in placental cells in the post-implantation embryo. Then I will evaluate how pregnancy progresses and the placenta functions when the setting of these epigenetic marks is disrupted. This study will provide ground-breaking insights into the fundamental mechanisms regulating placental development and demonstrate how these underpin its function in pregnancy.

Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: GENERIC HEALTH RELEVANCE;REPRODUCTIVE HEALTH AND CHILDBIRTH