A new Ph.D. project from Health, Aarhus University, explores how a mother's immune system affects her child's immunity and neurological development in the context of autoimmunity.

This Ph.D. defense investigates the complex interplay between maternal autoimmunity and fetal immunity, as well as the potential consequences for neurological development. The study utilizes mouse models of systemic lupus erythematosus (SLE) and employs both embryo-transfer techniques and a pristane-induced lupus model to distinguish genetic factors from influences of the maternal immune system.

These findings highlight that the maternal immune system plays a dual role in both transferring passive immunity and potentially imprinting the child's immune system. The study contributes valuable knowledge on how maternofetal immune interactions may impact the development of autoimmune diseases and neurological disorders in children.

A new PhD project from Aarhus University, Health, combines advanced tissue staining with AI-driven digital image analysis to develop a new digital tool for melanoma diagnostics.

The diagnosis of melanoma is challenging. Immunohistochemical biomarkers, such as Ki67, PRAME, and PD-L1, are often used to guide clinical decisions. However, interpreting these markers can be challenging because they are found not only in tumour cells but also in surrounding tissue. Traditional manual assessments can be time-consuming and prone to variation between pathologists. This project aims to develop a digital tool to help pathologists assess key biomarkers in skin cancer more precisely, enhancing diagnostic accuracy and reproducibility.

In this project, a double nuclear staining method was developed and combined with AI-driven digital image analysis into a tool that measures Ki67 and PRAME specifically in melanoma cells. The performance of this tool was evaluated in a cohort of challenging melanocytic lesions. Furthermore, the project explored whether this method could help predict patient outcomes for those receiving immunotherapy.

The proposed digital tool has the potential for clinical implementation, supporting pathologists with accurate, standardized, and reproducible biomarker measures to support the diagnoses of melanocytic lesions.

New PhD study highlights the need for screening of eating disorders in Danish adolescents with Type 1 Diabetes

A new Ph.D. dissertation is based on the 2-3-fold increased risk of eating disorders and disordered eating among ado-lescents with type 1 diabetes (T1D), aiming to investigate whether a simple systematic screening of these issues in youth is relevant in a Danish context.
The dissertation finds the Danish version of the questionnaire Diabetes Eating Problem Survey-Revised (DEPS-R) to be valid but also identifies limitations in detecting certain severe weight-regulating behaviors. The results show that more than 30% of young women with T1D exhibit signs of disordered eating (20% in the entire group) and that more than 30 % of adolescents in the study have experimented with severe weight-regulating behaviors within the past month.
Young people who participated in the screening were predominantly positive about using DEPS-R, as they recognized the issue in themselves or others, found that it encouraged reflection, and felt that DEPS-R opened the door to new relevant topics for discussion between themselves and healthcare professionals. This underscores the importance of us-ing screening tools in diabetes care. Furthermore, qualitative analyses highlight how diabetes management during adolescence can negatively impact body satisfaction and eating behavior.
The dissertation confirms the need to implement systematic screening to improve early detection and intervention, which may contribute to better health and quality of life for young people with T1D.

Advancing Stent Procedures with Better Imaging Techniques

This PhD study explores how advanced imaging can improve stent procedures for patients with complex coronary artery disease. The study, based on the OCTOBER trial, examines the role of optical coherence tomography (OCT) — a newer high-resolution imaging technique — in guiding these procedures compared to traditional X-ray-based methods.

The aims are to understand why some stent procedures fail, assess how well OCT guidance is followed in clinical practice, and determine whether traditional imaging techniques can provide equally reliable results. By addressing these questions, the study seeks to refine treatment strategies, improve procedural accuracy, and ultimately enhance patient outcomes.

The findings may help optimize the use of OCT in daily clinical practice, ensuring that heart patients receive safer and more effective treatments.

Post-stroke dementia is an important and common consequence of a stroke. Post-stroke dementia is associated with low quality of life and increased morbidity and mortality and thus poses a significant burden on patients and their caregivers. However, the risk factors for post-stroke dementia are still not completely understood. Determining risk factors for dementia among patients with acute stroke can be a first step towards finding preventive measures and treatments for post-stroke dementia.

To address this, we have conducted three nationwide register-based cohort studies of patients with acute stroke in Denmark. The studies linked data from Danish nationwide healthcare and administrative databases using the Danish Stroke Registry as the primary data source. We have examined whether treatment with intravenous thrombolysis of acute ischemic stroke is associated with the risk of post-stroke dementia, whether the incidence of post-stroke dementia differs among socioeconomic groups, and whether patients with acute ischemic stroke and atrial fibrillation have an increased risk of post-stroke dementia.

Mechanisms of Growth Hormone-induced Fibrosis in Human Adipose Tissue

Functional evaluation of intermediate coronary stenosis to guide revascularisation decisions is as sociated with improved patient outcomes and reduced number of stent implantations. However, the recommended pressure-wire-based method, fractional flow reserve (FFR), remains underuti lised. Quantitative flow ratio (QFR) is an angiography-based method for computation of FFR that does not require the use of pressure wires or medically induced hyperaemia. Whether QFR pro vides comparable prognostic benefit as FFR remains unknown.

Therefore we cundected a randomised multicentre trial. A total of 2,000 patients with intermediate coronary artery stenoses were randomly assigned to either a QFR-guided diagnostic strategy or an FFR-guided diagnostic strategy, followed by revascularisation of functionally significant lesions based on the diagnostic result. Moreover, a substudy was undertaken, in which we focused specifically on patients deferred from revascularization based on the QFR or FFR result.

Cancer is the leading course of death globally. It is effectively treated by radiotherapy, but as radiation damages healthy as well as tumour tissue, the overall aim of radiotherapy is to optimise the balance between tumour control and side effects. The location of the tumour and organs at risk are visualised just before treatment by scanning the patient on the treatment couch. Most modalities use X-ray CT, but the recent invention of integrating an MRI scanner with a linear accelerator, so-called MRI-guided radiotherapy (MRgRT), provides MRI images with enhanced soft tissue contrast and allows monitoring of internal organ motion. With these features MRgRT systems have the potential to optimize patient outcomes. 

Experimental validation of radiotherapy treatment plans is a prerequisite to ensure the quality of treatments and patient safety. Today, this is mostly done with point or planar measurements, however, the increased complexity of treatment delivery techniques demands 3D dose verification with high spatial resolution. The overall aim of this PhD thesis was to characterise a 3D silicone-based radiochromic dosimeter and to investigate its potential to validate dose distributions delivered by MRgRT systems.

In the first part of the study, a protocol for dosimeter fabrication was established. Subsequently, the dosimeter was characterised in MRgRT systems and a treatment plan was validated in 3D. Overall, the dosimeter showed clinical potential and applicability for dosimetric verification of treatment delivery of MRgRT systems.

The field of dentistry is continuously evolving to embrace the future. The changing needs of the population and society for dental care and technological advancements pose new demands on future dental care. To adapt to these changes, educating future dentists with a strong profile is essential, enabling them to make well-considered clinical decisions throughout their professional careers. In this profile, the ability to reflect and engage in self-directed learning is central to lifelong learning.

The purpose of the PhD project was to investigate the development of the dental curriculum. In addition, contribute to the knowledge of how learning tools such as reflective writing and multiple-choice questions (MCQ) can affect dental students' reflection and self-directed learning. To investigate this, we conducted three studies. First, we reviewed the literature for trends in curriculum development. In the second study, we examined dental students' perceptions of self-directed learning using MCQ as a learning tool. In the third study, we investigated whether reflective writing as a learning tool affects dental students' self-directed learning and reflective thinking ability.

There is a critical need to develop better medical treatments for patients with advanced cancer. Researchers are therefore working to find new ways to target cancer cells. In a new PhD project from Aarhus University, Martin Qvist Rasmussen has investigated two new potential targets for cancer treatment: the enzyme EGLN1 and the endocytic receptor LRP2.

Studies on the enzyme EGLN1 have shown that it plays an important role in the growth of melanoma cells. Inhibiting EGLN1, either genetically or with a drug, causes the cancer cells to stop dividing. This results from EGLN1 inhibtion altering the metabolism of cancer cells, limiting their ability to produce energy and molecules necessary for cell division. Drugs that inhibit EGLN1 have recently been clinically approved for the treatment of anemia in patients with chronic kidney disease. The results of this study therefore suggest that EGLN1 inhibitors could be repurposed as a potential new treatment for melanoma.

Studies on the endocytic receptor LRP2 have shown that it is highly expressed on the surface of cancer cells in several cancer types, particularly in mesothelioma. This discovery provided the basis for investigating LRP2 as a new target for drug delivery to cancer cells. To test this approach, monoclonal antibodies and antibody-drug conjugates against LRP2 were developed. These antibody-drug conjugates could selectively and effectively kill cancer cells expressing LRP2.

 The results of this PhD project provide the basis for further preclinical studies on EGLN1 inhibitors and LRP2-targeting antibody-drug conjugates as novel cancer treatments.

More than half a million Danes live with type 2 diabetes or ischemic heart disease, the vast majority of whom are treated in general practice. One in five patients also experiences poor mental well-being, such as depression or anxiety. This not only represents a significant burden for the individual but is also associated with poorer disease management and, ultimately, higher mortality rates.

In this Ph.D. study, we explored the use of problem-solving therapy in general practice. Initially, we investigated the feasibility of implementing this treatment in a general practice setting, and subsequently, we designed and conducted a randomized controlled trial to assess its effectiveness.

Citizens with screen-detected cardiovascular disease: Experience and adherence to preventive medication.    

This PhD project aims to gain insights into how citizens experience and adhere to recommendations for preventive medication for screen-detected cardiovascular disease (CVD), and how they are supported in their medication decisions.

CVD is the second leading cause of death in Denmark, with approximately one in four Danes dying from CVD each year. Research indicates that preventive medication for asymptomatic CVD, detected through screening, can reduce the risk and mortality of CVD, such as blood clots. However, there is a lack of knowledge about how citizens experience and adhere to recommendations for preventive medication initiated through screening. Additionally, there is a need for more insight into how citizens are supported in making informed medication decisions.

How does culture shape the way we hear, feel, and connect through music? This PhD project explores how cultural upbringing shapes not only our experience of music but also how we use it to engage with the world around us. 

Music is often called a universal language, but the way we listen, enjoy, and interact with it is deeply influenced by the culture we grow up in. This researcg takes the perspective of two distinct cultures, Denmark and China, to explore how culture shapes our relationship with music - and with each other through music.

The project includes five studies. The first three investigate how Danish and Chinese listeners perceive the three most fundamental components of music: rhythm, harmony, and melody. These studies reveal distinct cultural differences in what listeners find enjoyable and meaningful in their own and each other's musical traditions. Using behavioral and brain data, combined with advanced computational models, the research highlights how cultural upbringing influences not just our musical experiences but also how we make sense of the world around us.

The final two studies explore music’s social role, examining how cultural values shape our ability to synchronize and form emotional connections. By studying music cooperation and connection across cultures, the project highlights both what makes us different and what unites us.

Restoring STING and IFNλ signaling for anti-tumoral immunity using CRISPR activation

The cGAS-STING pathway is an immunological signaling pathway essential in th prevention of cancer. Activation of the pathway leads to the production of signaling molecules including interferons (IFNs), which can enhance antitumor immunity. However, suppressed STING expression is a common immune evasion mechanism in tumors, leading to reduced immune cell infiltration and weakened antitumor response. We developed a novel approach of increasing antitumor immunity by upregulating levels of the STING protein itself using CRISPR activation (CRISPRa). Although type I IFNs are commonly associated with STING activation, emerging research highlights the role of type III IFNs (IFNλ) in cancer immunity. IFNλ only affect a subset of cells and are thought to have fewer systemic side effects than type I IFNs which affect basically all cells. In lung cancer cell lines, we found that cGAS-STING pathway activation preferentially induced IFNλ. However, IFNλ signaling was impaired due to reduced expression of the receptor subunit IFNLR1. Using CRISPRa to restore IFNLR1 expression, we enhanced IFNλ signaling, leading to decreased cell viability and increased chemotherapy-induced apoptosis

Measurement and visualisation of the jawbone is required to replace missing teeth with dental implants. In some cases dentists can be dependent on scans with heavier radiation doses. In recent years a growing interest and technological advances has been seen in the field of magnetic resonance imaging, a scanning type free from radiation. A new PhD project from Aarhus University, Health, investigates the precision by which jawbone measurements can be achieved using this technology as compared to conventional X-ray based scans.

In the first part of the project the existing literature was reviewed to establish the state of affairs. This lead to two articles pinpointing strengths, weaknesses, and raised new questions regarding the potential of magnetic resonance imaging in dentistry.

In the second part of the project laboratory scans of human jaws was performed using magnetic resonance imaging technology to compare scans acquired with this relatively new technology to those from an older, radiation-based technology. During this period the method was refined and further parameters were introduced. This lead to two research articles.

The results of the project helped creating a model to measure and discuss bone measurements performed using magnetic resonance imaging in a controlled setup. It was shown that jawbone measurements could be performed with similar precision utilizing the two different methods of imaging: with and without exposure to ionising radiation.

The innate immune system recognizes bacteria using specialized molecules. The immune system relies on pattern recognition molecules (PRMs) and receptors (PRRs) to identify specific carbohydrate patterns on bacterial surfaces. These interactions help trigger immune responses, including the complement system, which fights infections. The focus of this PhD project has been to investigate these carbohydrate binding PRMs and PRRs an how they recognize various bacterial carbohydrate patterns.

In one study it was investigated how PRMs of the complement system like mannan-binding lectin (MBL) and ficolins bind to components of Gram-negative bacteria, such as lipopolysaccharides (LPS). These molecules recognized the O-antigen part of LPS, with unique binding patterns for each PRM. Experiments showed that factors like bacterial structure and environment also influence binding.

Another part of the project examined the interactions between C-type lectins (MBL, Surfactant protein-D, and langerin) and the Gram-positive bacterium Staphylococcus aureus specifically evaluating two carbohydrate structures Capsular polysaccharide (CP) and wall teichoic acid (WTA). S. aureus can produce CPs that impaired recognition by all three C-type lectins. While MBL binds to WTA, Langerin appeared to recognize additional bacterial components on the surface of S. aureus

Developmental transdiagnostic mechanisms underlying Functional Somatic Symptoms

Functional Somatic Symptoms (FSS) correspond to those physical symptoms like headaches, abdominal pain and fatigue, that can commonly not be attributed to a well-defined somatic condition. FSS are common in young people, and global prevalence rate of any kind of FSS estimates 31% to be affected. The etiology underlying FSS is suggested to be complex and multifactorial, involving various interacting biopsychosocial risk factors and mechanisms to placed young people at risk for developing FSS already at a young age. This project from Aarhus University, Health, offers new insights into child- and familial- risk factors for FSS at various developing developmental stages. Further, the project shows developmental symptom paths and highlights co-occurring psychopathology during adolescence, and emphasizes potential new avenues for preventive measures.

Gestational diabetes is a temporary form of diabetes that can develop during pregnancy, posing significant health risks for both mother and child in the short and long term. While there has been considerable progress in understanding the physiological aspects of gestational diabetes, less attention has been given to the psychosocial aspects, particularly the stigma experienced by women with gestational diabetes.

This PhD project investigated the stigma associated with gestational diabetes through four studies: a literature review, a qualitative interview study, a psychometric scale validation study, and a quantitative association study. One of the key findings is that women with gestational diabetes, both in Denmark and globally, may feel stigmatised due to their diagnosis. This includes experiences of negative treatment from healthcare professionals and close family members, which can lead to feelings of guilt and shame about their condition. As a consequence, some women reported avoiding disclosing high blood sugar levels or declining gestational diabetes screening in future pregnancies. These findings highlight the need for further systematic research into the stigma associated with gestational diabetes, the consequences, and potential strategies to reduce the stigma experienced by women with gestational diabetes.

Laurits Taul-Madsen, 
Department of Public Health 

Long-term effects of exercise on physical function in people with multiple sclerosis – the effect of exercise booster sessions

Multiple Sclerosis (MS) is a neurodegenerative disease affecting approximately 19.000 people in Denmark. MS presents with a broad range of symptoms, with one of the most frequently reported being loss of physical function. However, one of the most promising strategies to improve this specific symptom, and many others, is exercise. Nevertheless, sustaining an adequate level of exercise over time can be challeging. Therfore, the present study aimed to investigate the term effects of exericse by applying so called exercise booster sessions.

The project explores how the brain processes and remembers music, focusing on long-term memory and aging. While memory has been widely studied in visual tasks, this work dives into the lesser-explored auditory domain, especially music. Using advanced brain imaging techniques and cognitive tests, it investigates how we encode, store, and retrieve musical memories, how different auditory memory systems interact, and how aging affects these processes. Key results revealed that musical memory relies on the hierarchical interplay between brain regions involved in audition, memory, and decision-making, that working memory abilities and musical complexity are associated with better recall of musical sequences, and that healthy older adults recruit compensatory brain mechanisms to support recognition of musical sequences. Overall, this PhD dissertation advances our understanding of auditory memory and provides novel insights into cognitive aging.

External cervical resorption: Prevalence in adolescents, radiographic diagnosis and long-term prognosis

External Cervical resorption (ECR) is a pathologic condition in teeth, which damages the hard tissue. Over time, ECR risk progression and can lead to tooth loss. ECR is often detected by incident in radiographs, since ECR mostly appear asymptomatic. A new PhD project from Aarhus University, Health investigates the effect of two-dimensional (2D) and three-dimensional (3D) radiographic methods in diagnosing and assessing long-term prognosis of ECR.

In the first part of the project, a group of adolescents was examined to estimate the prevalence of ECR in posterior teeth in 2D and 3D radiographs. A small fraction of patients showed sign of ECR in 2D radiographs and therefore 3D radiographs were performed. The conclusion was that only a low number of patients were diagnosed with ECR.

The second part of the project, focused on comparing the severity of ECR in teeth in a group of referred patients based on 2D and 3D radiographs. The 3D radiographs showed more severe extension of ECR in more than one third of the cases compared to 2D radiographs.

In the third part of the project, a group of referred patients were examined in order to assess long-term prognosis for teeth with ECR in the same two radiographic modalities. The results showed that in almost one third of the cases long-term prognosis changed based on additional information from 3D radiographs. 

This PhD study explores the research opportunities of using existing data to follow children with obesity in a real-life setting. The aim was to investigate the long-term effect of already implemented municipality-driven lifestyle interventions and to better understand mechanisms related to the weight development in children already classified as having obesity.

The PhD study was conducted by combining the national registers with measures of weight and height obtained at the schools, hereby allowing the researchers to follow the individual child throughout childhood.

Management of bowel dysfunction following treatment of pelvic organ and colon cancers

The increasing number of cancer survivors in Denmark and globally has highlighted a critical need for dedicated rehabilitation services to address late sequelae from treatment. While many cancer survivors live with lasting physical and psychological effects, access to specialized rehabilitation services remains limited. In Denmark, national efforts, including the integration of survivorship care plans, have aimed to address these gaps in cancer care.

This dissertation examines the challenges faced by pelvic organ and colon cancer survivors, particularly those who experience late bowel dysfunction—a common and complex issue that diminishes quality of life for many patients. This research is part of a broader initiative led by the Centre for Research on Survivorship and Late Adverse Effects after Cancer in the Pelvic Organs, which was established to improve support for survivors through the creation of specialized late sequelae clinics. These clinics, founded in 2017 and 2018, employ multidisciplinary, algorithm-based approaches to address the diverse needs of patients with bowel dysfunction.

Through studies conducted within these clinics, this thesis investigates the effectiveness of specialized, patient-centered care in managing complex gastrointestinal sequelae. Findings aim to inform future cancer rehabilitation efforts by identifying effective treatment modalities and improving our understanding of the physiological mechanisms underlying these sequelae.

Heart disease is a significant threat to individuals with chronic kidney disease (CKD), especially those with severe CKD or kidney failure. In particular, coronary artery disease (CAD) plays a critical role in raising the risk of heart attacks and mortality in this group. Therefore a new PhD project at Aarhus University, Health investigated CAD among patients with severe CKD using coronary computed tomography angiography (CCTA).

The PhD project analyzed data from three historical patient cohorts in Western Denmark (2008-2021), with the majority of studies focusing on potential kidney transplant candidates. The findings reveal that patients with reduced kidney function show increased signs of adverse CAD characteristics, including high-risk plaques, higher burdens of calcified and non-calcified plaque, and impaired coronary flow which elevate the likelihood of heart attacks and other cardiac events. The project also indicated a low usage of systemic medical therapy among patients with reduced kidney function, despite the increased risk of cardiac events among these patients.  This research suggests that by leveraging CCTA, healthcare providers may better evaluate and address heart disease risk in CKD patients, especially in those being evaluated for kidney transplantation. Furthermore, it underscores the heightened cardiac risk in patients with reduced kidney function, and the need for optimizing and developing systemic preventive therapy in such patients

Rethinking Ethylmalonic Encephalopathy
Ethylmalonic Encephalopathy (EE) is a rare disorder caused by an inability to break down sulfide, a natural chemical that in normal levels helps relax blood vessels. In EE, sulfide builds up to toxic levels, blocking the body’s energy production and causing serious symptoms early in life. The project explored the use of cobinamide, a natural compound related to vitamin B12, to clear excess sulfide from the body. In laboratory and animal models, cobinamide has shown potential in neutralizing sulfide safely. However, despite its success in these models, cobinamide had limited effect in tests with cells and mice affected by EE. This unexpected result led to a re-evaluation of what drives EE, suggesting that the disease may involve more than just sulfide buildup and highligting new mechanisms that might give rise to the symptoms. This research could open new directions for understanding and treating EE by focusing on other underlying mechanisms of the disease.

Protecting Brain Health in Alzheimer’s Disease
Alzheimer’s disease is often accompanied by accumulation of protein debris around brain blood vessels. This can worsen disease progression and complicate treatment. To understand the effects of this buildup, brain tissue from a mouse model that mimics this disease feature was examined. To counteract these damaging changes, a class of well tolerated drugs used for treating mountain sickness and glaucoma, was tested. Remarkably, in agreement with recent reports, both drugs from this class reduced many of the harmful protein changes, helping to preserve vital brain connections in the Alzheimer’s model. This suggests that these repurposed drugs could be effective in slowing down the disease’s progression by maintaining brain health longer, potentially offering a new avenue for Alzheimer’s treatment.

Long COVID is a global health issue, and up to 10% of individuals infected with SARS-CoV-2 develop prolonged symptoms. There is currently no treatment, and the reason why some develop long-term effects is unknown. This project includes the world’s first treatment with a medication targeting long COVID. Furthermore, the project examines the presence of specific antibodies against the patient's own immune system and explores a genetic basis for the development of long-term effects after COVID-19.

Axial spondyloarthritis pathogenesis remains poorly understood and is difficult to diagnose in the early stages of the disease. While effective therapy is available, early disease identification continues to pose a challenge. The PhD study explores the complement system concerning diagnosis, disease activity, treatment response, and radiographic progression in patients with axial spondyloarthritis. The research involves cross-sectional and longitudinal cohorts conducted in collaboration with partners at COPECARE, CeVig, and Charité.

Endothelial cells (ECs), which line blood vessels, are essential in regulating immune responses by facilitating the passage of immune cells from the bloodstream to infection sites. This process increases vessel permeability and requires the rearrangement of junctional proteins between ECs, the expression of adhesion markers on their surface, and the release of inflammatory molecules. Moreover, these changes often require metabolic shifts in the ECs to support their activated state.

Coronary Magnetic Resonance Angiography (CMRA) is a non-invasive modality that can investigate Coronary Artery Disease (CAD) without the use of ionising radiation or iodinated contrast agents. However, prior clinical use has been inhibited by the long acquisition times, substantial technical expertise requirements and comparatively poor spatial resolution compared to other methods. Development of deep learning (DL) based automated software for planning and acquisition may overcome some of these challenges.

Epstein-Barr virus (EBV) is associated with the development of a wide range of cancers, including post-transplant lymphoproliferative disorder (PTLD) among solid organ transplant recipients. Consequently, screening for EBV-DNA in blood compartments (EBV-DNAaemia) is now included in international guidelines for transplant recipients. However, the clinical significance of EBV-DNAaemia in plasma and whole blood is yet to be determined, and evidence-based therapeutic preventive strategies against PTLD remain scarce.

This PhD project aimed to investigate 1) the clinical spectrum of EBV-associated disease in patients from the Central Denmark Region and to assess the diagnostic accuracy of EBV-DNAaemia in this population, 2) to estimate the incidence and risk factors for PTLD in EBV-seronegative kidney transplant recipients in the contemporary era of immunosuppression, and 3) to investigate the incidence of EBV-DNA in both plasma and whole blood as a predictor for PTLD in kidney transplant recipients.

Malnutrition requiring hospitalization, among children under 5 years of age, remains a major problem globally. Mortality is high and up to 2 out of 10 children die during hospitalisation. If this high mortality is to be lowered, it is necessary to find new treatment strategies to improve hospital management. The acute malnourished children can develop severe wounds and peeling of the skin, among other things. This is a symptom of malnutrition for which the cause is not yet known and for which the World Health Organization's (WHO) treatment guidelines do not yet provide an evidence-based management.

This PhD study is an investigation of skin changes in severe acute malnutrition. Published knowledge is reviewed, nomenclature is established and a scoring tool for clinical documentation of the skin changes is developed through a prospective observatory study. The prognostic effect of the skin changes is investigated and an exploratory study of the immune status of the patient group is included. Finally, a qualitative study of the challenges among health personnel illustrates the use of methods from health anthropology to identify the local agenda within the subject.

Coronavirus infections typically give rise to common cold symptoms. However, rare viral variants emerge, causing severe respiratory disease. At the outbreak of the SARS-CoV-2 pandemic in 2020, the lack of specific prophylactic and therapeutic treatment options was limiting for patient care. This PhD thesis explores the development of novel SARS-CoV-2 specific monoclonal antibodies for SARS-CoV-2 prophylaxis, through three stages: 1) Discovery of neutralizing monoclonal antibodies from convalescent individuals. 2)  In depth characterization of antibody potency, sensitivity to viral variants, and therapeutic potential of preventing infections in mice. 3) Investigation of the possibility of delivering antibody genetic sequences through Adeno Associated Virus for long-term expression and passive immune-prophylaxis.

Chronic cluster headache ranks among the most severe pain conditions known to man. Patients experience excruciatingly painful headache attacks, often described as a knife stabbing the eye. Sometimes, patients suffer from these headache attacks multiple times a day. For some patients, the conventional medical treatment options fail to provide sufficient relief. For this group of patients, a treatment modality called neuromodulation may be an option. Neuromodulation is a therapy where a nerve structure stimulated by weak electrical currents. Several smaller studies have shown that electrical stimulation of the so-called occipital nerves at the back of the head - occipital nerve stimulation (ONS), where a stimulation electrode in implanted under the scalp - can prevent the painful cluster headache attacks in patients where other treatment options seem exhausted.

A new Ph.D. project from Aarhus University, Health, systematically investigates the effect of ONS as a preventive treatment for patients with severe chronic cluster headache. The dissertation presents a database study of the clinical effect on patients already undergoing ONS treatment. It also includes an examination of the efficacy of a simpler, non-invasive stimulation, where the occipital nerves are stimulated through the skin of the scalp, and whether the effect of this transcutaneous stimulation can predict the effect of the implanted ONS electrode. 

Hip fracture is a devastating and common injury among older adults. The incidence rate of hip fracture in Denmark is among the highest globally and has increased in recent years. Despite infection being a potentially preventable and treatable condition, it remains one of the most frequent complications and causes of death following hip fracture surgery. Risk of infection after hip fracture has also increased.

What determines if the immune system can attack cancer cells? And how can we support it? This has been investigated in a new PhD project from Aarhus University, Health. 

The immune system plays an important role in cancer and represents a potential source of future treatments. One the constituents of the immune system, cells known as macrophages, are able to attack and kill cancer cells under the right conditions. This PhD project has investigated which factors regulate the ability of macrophages to destroy cancer cells, and how these factors can be medically influenced. The results of the project suggest that new techniques can potentially be used to support macrophage killing of cancer cells, and are based on laboratory experiments performed at the Department of Clinical Biochemistry at Aarhus University Hospital.

Follicular lymphoma (FL) is a lymphoid malignancy derived from germinal center B cells. Despite advancements in treatment, the disease remains generally incurable with recurrent relapses. Furthermore, a subset of patients will experience treatment refractoriness, early disease progression, and histological transformation into a more aggressive lymphoma type, most often diffuse large B-cell lymphoma. This event is manifested by a rapid clinical course, often with unresponsiveness to treatment, and shortened survival. Thus, transformation marks a pivotal change in disease trajectory, yet reliable predictors for subsequent progression or transformation remain elusive.

This Ph.d. project describes the transformation of FL, with the aim to unravel pre-treatment biological differences underlying the diverse disease course for upfront personalized risk stratification and improved patient care.

The dissertation comprises eight original papers. These include several molecular biological investigations of proteins and gene expression thoroughly examined in relation to transformation of FL, revealing predictive potential of several proteins in the neoplastic cells as well as the tumor microenvironment.

Workplace intervention to reduce sick leave among pregnant hospital employees – a cluster randomized trial.

In a recently completed Ph.D. project from Occupational Medicine, Aarhus University Hospital and Aarhus University, Jane Lauridsen evaluated an intervention with occupational midwifery support on pregnant employees' sick leave and well-being.

Sick leave during pregnancy is common and 36% of all pregnant employees are absent for more than two weeks. Sick leave can be associated with individual and occupational factors. Occupational factors can be exposure to harmful agents or strenuous working conditions such as walking and standing, heavy lifting, or shift work. Work adjustment is associated with reduced sick leave.
This project evaluates an intervention aiming to reduce strenuous occupational exposures. The overall aim was to evaluate the effect of occupational midwifery support, where midwives facilitated risk assessment and work adjustment in meetings with pregnant employees and their managers.
The study was conducted at Aarhus Universityhospital as a cluster-randomised trial with hospital departments allocated to intervention or reference.
In addition to evaluating midwifery support, the projct also investigated managers´ perspectives and engagement in pregnancy policy.

The intricate interplay between inflammatory bowel disease (IBD), cancer, infections, and mortality is explored in a new PhD project at Aarhus University, Health.

IBD are chronic, immune-mediated inflammatory disorders encompassing Crohn’s disease and ulcerative colitis. Patients with IBD face an increased risk of developing colorectal cancer, as well as several other types of cancer.

When patients with IBD develop colorectal cancer, their prognosis is typically worse compared to those without IBD, which may be exacerbated by their inherent increased risk of infections. Serious infections are a leading cause of hospitalization and mortality among IBD patients. Moreover, infections account for more than half of all oncology-related hospital admissions, negatively affecting cancer-specific survival rates.

This PhD project provides novel insights into the association between IBD and post-cancer infection risk, as well as the link between IBD and post-colorectal cancer mortality, based on data from a Danish cancer cohort.

Broadly neutralizing antibodies (bNAbs) are being used in clinical studies which seeks to lower the viral reservoir in persons living with HIV-1. bNAbs have shown to be able to neutralize cell-free virusparticles and activate the immune system and thereby increase the pressure on HIV-1 infected cells. Due to a high mutation rate in HIV-1, the bNAbs do not have an effect in all persons living with HIV-1, which makes it important to screen virus from the participants prior to inclusion in a study using bNAbs. 

In this PhD project a published clinical study is presented, in which persons with HIV-1 were randomised to receive two bNAbs and a drug (Lefitolimod), which have shown to reactivate virus in HIV-1 infected cells. The participants stopped their normal antiviral treatment and the study showed that participants who received the bNAbs had longer time before virus was detectable in the blood, than participants who did not receive the bNAbs.  

Addtionally, a study in which methods to screen participant-specific HIV-1 for sensitivity toward the bNAbs were compared. The study showed that there can be differences in the methods which are being used for sensitivity assessment for the bNAbs.

Fluorescence Microscopy of the Living Kidney to Visualize and Understand Renal Physiology

The dissertation is centered around a cutting-edge microscopy technique that allows the real-time visualization and assessment of kidney function in living small rodents. The research introduces key advancements aimed at overcoming the challenges of data acquisition and processing in this complex field. In addition, the study highlights two practical applications of this technology, offering new insights into renal physiology and potential implications for future medical research.

Diabetic polyneuropathy is a common and debilitating complication to diabetes that affects up to 50% of all patients with diabetes. It affects the long nerves of the body, causing loss of sensation as well as unpleasant sensory disturbances in the feet and legs. Between 10-35 % of patients with diabetic polyneuropathy suffer from pain. It is currently unknown what causes pain to develop. This condition, especially with concurrent pain, impacts the quality of life of patients in various negative ways, and no satisfactory treatment exists. Despite this, diabetic polyneuropathy has often been considered an overlooked complication to diabetes, which may be the reason that there are few detailed studies on its development over time.

This PhD project followed patients with diabetic polyneuropathy and type 2 diabetes over five years using state-of-the-art diagnostic methods to determine how both diabetic polyneuropathy and pain develops over time, which patients develop pain, what impacts this development, and how these changes affect patient quality of life and mental health.

Autoimmune diseases are rising in society and a huge burden to patients. The main characteristic shared by all of them is the patient’s own immune system attacking the body and damaging organs, up to the point of failure. However, current treatment options are limited and come with severe side effects such as infections and even cancer.

The development and progression of autoimmune diseases is complex, long-lasting and not fully understood – including the emergence and shutdown of autoreactive germinal centers, which are presumably contributing to disease progression, especially the germinal centers in the spleen.

The emergence and shutdown of germinal centers are week-long dynamic processes and therefore difficult to capture and understand. Thus the development of novel techniques is necessary to study germinal center dynamics to help understand the development and progression of autoimmunity to one day hopefully being able to develop better treatment.

In my PhD defense, I will present a newly developed and validated approach to study autoreactive germinal center dynamics over two weeks in a living organism by using serial intravital microscopy of the spleen. I will furthermore present how we are exploiting this technique to shed more light on the development of autoimmunity.

A positive screening test for colorectal cancer, but no cancer - What now?

In a recently completed Ph.D. project from Aarhus University and Randers Regional Hospital, Pernille Thordal Larsen investigated how many people are diagnosed with colorectal cancer after initially being screened without any findings of cancer. 

The evidence supporting the Danish recommendations for follow-up after a screening-derived colonoscopy is limited, despite the fact that since 2014, these recommendations for colonoscopy follow-ups have led to a significant increase in the number of colonoscopies performed in Denmark. This Ph.D. project utilized Danish health registers and databases to investigate how many people are diagnosed with cancer after initially undergoing a screening process that did not result in a cancer diagnosis. The project found that, in general, there were few cases of cancer, but the number of polyps found during the colonoscopy was a poor indicator of the risk at the next screening or follow-up examination. Therefore, it is concluded that screening recommendations should be based on risk factors that consider more than just the results of the colonoscopy, and further efforts should be made to ensure high-quality colonoscopies for all screening participants in Denmark.

Towards more accurate and gentle surgery for women with endometrial cancer - The SENTIREC-endo study

In endometrial cancer, the presence of lymph node metastasis is the most significant negative prognostic factor. Surgical staging is performed to identify women with lymph node metastasis to allocate them to adjuvant therapy, with the overall purpose to improve survival. Sentinel lymph node (SLN) mapping represents an accurate and minimally invasive staging technique, with the potential to increase the identification of lymph node metastases. This PhD thesis is based on two national prospective studies, SENTIREC-endo I and II, that investigated aspects of SLN mapping implementation in women with endometrial cancer. SENTIREC-endo I presents the result of a national protocolled implementation of SLN mapping in women with low- and intermediate-risk endometrial cancer. We conclude that SLN mapping, in a centralized setting, carries a very low risk of peri- and postoperative complications and that women benefit from the procedure in terms of increased detection of lymph node metastases compared to previous standards. Despite more comprehensive surgery for a large proportion of women, SLN mapping was not associated with an increased risk of clinically significant lymphoedema. SENTIREC-endo II, investigated diagnostically safe SLN mapping algorithms to replace the standard of pelvic and paraaortic lymphadenectomy in women with high-risk endometrial cancer. We identified two safe surgical algorithms. The SENTIREC-endo studies have changed clinical guidelines towards more gentle and accurate surgery for women with endometrial cancer and lead to new international evidence.

Tuberculosis is an infectious disease that is especially prevalent in low-income countries, where poverty and crowded living conditions contribute to disease transmission. Although tuberculosis can be cured with antibiotics, it is estimated that over 10 million people develop tuberculosis, and over 1 million people die from tuberculosis every year worldwide.

Malnutrition, especially undernutrition, is a well-known risk factor for developing tuberculosis. An insufficient intake of energy, protein, and micronutrients, weakens the immune system and thereby increases the risk of developing tuberculosis. Malnutrition may be a result of food insecurity in low-income countries. Furthermore, tuberculosis disease causes malnutrition through various disease-specific effects on the body. It is often difficult to ascertain which comes first - malnutrition or tuberculosis - and which makes the other worse.

The West African country Guinea-Bissau is one of the poorest countries in the world. It has a high prevalence of both food insecurity and tuberculosis. The Ph.d. project explores the relationships between malnutrition and tuberculosis in Guinea-Bissau, and examines if a combined treatment of both malnutrition and tuberculosis is beneficial to patients.

Fernando Valentim Bitencourt, Department of Dentistry

The prevalence of periodontitis, an inflammatory condition that affects the tissues supporting teeth, is three times greater in individuals with Type 2 Diabetes Mellitus (T2DM) than in those without T2DM. Despite this prevalence, the relationship between periodontitis and diabetes-related complications has remained unclear until now. The PhD studies, conducted through population-based studies, analyzed data from participants across US and Denmark: the National Health and Nutrition Examination Survey (NHANES) and the Health in Central Denmark (HICD) study. The findings reveal that periodontitis co-occurs with other diabetes-related complications, influenced by factors such as age, sex, obesity, physical activity, diet, socioeconomic status, smoking, HbA1c levels, and dyslipidaemia. The study also demonstrated that higher HbA1c levels and obesity had a significant indirect effect on periodontitis through dyslipidaemia. In addition, diabetic retinopathy, neuropathy, and both complications increase the likelihood of developing periodontitis by 1.2 to 1.5 times. Furthermore, dyslipidaemia was shown to significantly modify the odds of 'moderate/severe' periodontitis, particularly when multiple diabetic microvascular complications are present.

Faecal microbiota transplantation (FMT) involves the transfer of intestinal microbiota from a healthy donor to a patient. The choice of donor is crucial to ensure a safe and possible also effective treatment. Despite this, faeces donation criteria are not based on evidence.

The aim of this project was to produce knowledge that will contribute to establishing evidence-based criteria for faeces donation. A wide range of donor criteria are addressed, including gastrointestinal symptoms and bowel habits, asymptomatic Helicobacter pylori carriage, and an assessment of whether donor factors affect the clinical effect of FMT in patients with Clostridioides difficile infection.

Screening for breast, colorectal, and cervical cancer can reduce morbidity and mortality from these three types of cancer, but participation in the three national screening programmes varies.

The aim of the PhD project was to investigate cross-programme synergies and correlations across the three cancer screening programmes in Denmark.

In a clinical intervention study, women attending breast cancer screening in the Central denmark Region were offered an administrative check-up on their screening status for cervical and colorectal cancer. Women who were not up-to-date with their screenings were subsequently offered the opportunity to perfom self-collected screening for cervical and colorectal cancer.

In two register-based studies, the relationship between screening participation and both sociodemographic data and level of health literacy was examioned to better understand the characteristics of those who do not participate in all three screening programmes.