BACKGROUND: Melanoma is a highly heterogeneous disease, and a deeper molecular classification is essential for improving patient stratification and treatment approaches. Here, we describe the histopathology-driven proteogenomic landscape of 142 treatment-naïve metastatic melanoma samples to uncover molecular subtypes and clinically relevant biomarkers.METHODS: We performed an integrative proteogen

This article is based on the author's involvement in preparing a Draft Statute for a future World Court of Human Rights. The proposal seeks to modify the traditional vertical structure of human rights norms by introducing a mechanism for adjudicating claims about human rights violations by actors other than states, including by international organizations (IO) or transnational corporations (TNC).

Introduction: The pulmonary oxygen uptake is reduced during apnea, compared to eupneic baseline, preserving the pulmonary oxygen store. This study elucidates the time course for this reduction, comparing it to the time course for apnea-induced cardiovascular responses. Methods and results: Experiments involved two groups, performing apneas during rest, both without and with cold-water face immersi

In situ X-ray reciprocal space mapping was performed during the interval heating and cooling of InGaN/GaN quantum wells (QWs) grown via metal–organic vapor phase epitaxy (MOVPE). Our detailed in situ X-ray analysis enabled us to track changes in the peak intensities and radial and angular broadenings of the reflection. By simulating the radial diffraction profiles recorded during the thermal cycle

SARS-CoV-2 can cause clinical and inapparent disease and mortality in several animals cohabitating with humans, and sheep are susceptible to SARS-CoV-2 due to virus–receptor interactions similar to those in humans. Hence, sheep have the potential to be infected, spread, and develop neutralising antibodies (NAbs) against SARS-CoV-2. The aim of this study was to investigate the prevalence of SARS-Co

The human gut microbiome is a highly complex environment, where a myriad of intricate microbiota-microbiota and microbiota-host interactions occur. The human gut microbiota has been associated with both health and disease. The research presented in this thesis focuses on investigating how the butyrate-producing human gut bacterium Roseburia hominis A2-183 (R. hominis) processes β-mannan oligosacch

The first years of life are a critical period of development, and circumstances during this period can affect individuals throughout life. But to what extent do disadvantaged circumstances in childhood affect individual wellbeing in later life and for whom? Can interventions in childhood break adversity over the life course? For whom are interventions most effective and why?This thesis aims to invThe first years of life are a critical period of development, and circumstances during this period can affect individuals throughout life. But to what extent do disadvantaged circumstances in childhood affect individual wellbeing in later life and for whom? Can interventions in childhood break adversity over the life course? For whom are interventions most effective and why? This thesis aims to in

The impact of islet neuronal nitric oxide synthase (nNOS) on glucose-stimulated insulin secretion (GSIS) is less understood. We investigated this issue by performing simultaneous measurements of the activity of nNOS versus inducible NOS (iNOS) in GSIS using isolated murine islets. Additionally, the significance of extracellular NO on GSIS was studied. Islets incubated at basal glucose showed modes

The discovery of exoplanets has revealed an intriguing class of planets unlike anything in the Solar System: ultra-hot Jupiters. These gas giants share similarities with Jupiter in size and in their hydrogen- and helium-dominated atmospheres, yet their proximity to their host stars results in vastly different atmospheric conditions. Intense stellar radiation heats them to temperatures exceeding 20

Particulate methane monooxygenase (pMMO) is the most efficient of the two groups of enzymes that can hydroxylate methane. The enzyme is membrane bound and therefore hard to study experimentally. For that reason, there is still no consensus regarding the location and nature of the active site. We have used combined quantum mechanical and molecular mechanical (QM/MM) methods to study the reactivity

The European Union member states received about 385,000 asylum applications from children and adolescents below 18 years in 2015, and 398,000 in 2016. The latest political crises and war have led to an upsurge in refugee movements into European countries, giving rise to a re-evaluation of the epidemiology of psychiatric disorders and mental health problems among young refugees and asylum seekers.

Extracellular vesicles (EVs) carry biological information from their parent cell to other cells in the body. To intercept and decipher this information necessitates the isolation of EVs from complex backgrounds such as blood or spinal fluid. Acoustic trapping has been previously demonstrated as a promising technique for EV isolation from cell media, blood plasma and urine. The acoustic fields stru

Background Our aim was to evaluate if increased survival and new ventilation strategies were accompanied by a changed incidence of bronchopulmonary dysplasia (BPD) in Sweden over a decade. Methods Data from two Swedish population-based studies of live-born infants with gestational age (GA) 22–26 weeks, born during 2004–2007 (n=702) and 2014–2016 (n=885), were compared for survival, any BPD, modera

The KEYNOTE-564 trial showed that adjuvant immune checkpoint inhibitor (ICI) therapy with pembrolizumab, a PD-1 antibody, significantly improved disease-free survival (DFS) and overall (OS) survival in localised clear-cell renal cell carcinoma (RCC) with a high risk of relapse. The TiNivo and CONTACT-03 trials have reported results for subsequent therapy after progression on ICI therapy in the met

Achieving good acoustic particle or cell separation performance requires skilled operators, who must carefully fine-tune the input parameters (actuation voltages, flow rates, and flow split ratios). Often the fine-tuning is done by time-consuming parameter sweeps, which are tedious and expensive. Here, we present a straightforward model-based approach to determining input parameters that yield opt

Varje cell i kroppen bär på drygt tjugotusen gener som ärvs från föräldrarna och som fungerar som instruktioner för att producera kroppens olika proteiner. Gener har en bestämd sekvens för att deras protein ska uppfylla rätt funktion men när cellerna delar på sig eller utsätts för yttre faktorer såsom strålning eller giftiga kemikalier kan en mutation uppstå. Det felaktiga proteinet kan ge upphov Background: The utility of whole-genome sequencing (WGS) in diagnosing cardiomyopathies (CM) and heritable connective tissue disorders (HCTD) is limited by high costs and ambiguous results. Letting the referring physician decide whom to refer for WGS increases the absolute number of positive patients identified but lowers clinical yield (proportion of patients identified with a pathogenic gene var

Background: Malignant hyperthermia (MH) susceptibility is associated with variants in RYR1, the gene encoding the skeletal muscle ryanodine receptor-1 (RyR1), in 70–75% of patients. Functional characterisation demonstrating an increased sensitivity to RyR1 agonists is necessary among other criteria for inclusion in the European Malignant Hyperthermia Group list of MH susceptibility diagnostic vari