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Stem cell therapies for neurological disorders are rapidly moving towards use in clinical trials. Before initiation of clinical trials, extensive pre-clinical validation in appropriate animal models is essential. However, grafts of human cells into the rodent brain are rejected within weeks after transplantation and the standard methods of immune-suppression for the purpose of studying human xenog
Background and aimsElevated body weight in adolescence is associated with early cardiovascular disease, but whether this association is traceable to weight in early adulthood, weight in midlife or to weight gain is not known. The aim of this study is to assess the risk of midlife coronary atherosclerosis being associated with body weight at age 20, body weight in midlife and body weight change.Met
Aims: Exhaled breath particles have been explored for diagnosing different lung diseases. We recently showed in an experimental model that different cardiac output results in different particle flow rate (PFR) from the airways. Given the well-known close relationship between impaired cardiac function and respiratory failure, we hypothesized that PFR in exhaled air can be used to detect cardiac fai
Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the t
Objective: To assess the proportion of participants reconsidering their willingness to undergo surgery after 3 and 12 months. Secondary aims were to analyze and compare the characteristics of individuals willing and unwilling to undergo joint surgery for osteoarthritis (OA) before a first-line intervention, and to study the association between pain intensity, walking difficulties, self-efficacy, a
Astrocytes are essential cells for normal brain functionality and have recently emerged as key players in many neurological diseases. However, the limited availability of human primary astrocytes for cell culture studies hinders our understanding of their physiology and precise role in disease development and progression. Here, we describe a detailed step-by-step protocol to rapidly and efficientl
Recent advances in genome editing have brought new hopes for personalized and precision medicine but have also dramatically facilitated disease modeling studies. Combined with reprogramming approaches, stem cells and differentiation toward neural lineages, genome engineering holds great potential for regenerative approaches and to model neurological disorders. The use of patient-specific induced p
Well-characterized archival formalin-fixed paraffin-embedded (FFPE) tissues are of much value for prospective biomarker discovery studies, and protocols that offer high throughput and good reproducibility are essential in proteomics. Therefore, we implemented efficient paraffin removal and protein extraction from FFPE tissues followed by an optimized two-enzyme digestion using suspension trapping
Three-dimensional brain organoids have emerged as a valuable model system for studies of human brain development and pathology. Here we establish a midbrain organoid culture system to study the developmental trajectory from pluripotent stem cells to mature dopamine neurons. Using single cell RNA sequencing, we identify the presence of three molecularly distinct subtypes of human dopamine neurons w
Coherent X-ray imaging techniques, such as in-line holography, exploit the high brilliance provided by diffraction-limited storage rings to perform imaging sensitive to the electron density through contrast due to the phase shift, rather than conventional attenuation contrast. Thus, coherent X-ray imaging techniques enable high-sensitivity and low-dose imaging, especially for low-atomic-number (Z)
The tumor microenvironment plays an essential role in supporting glioma stemness and radioresistance. Following radiotherapy, recurrent gliomas form in an irradiated microenvironment. Here we report that astrocytes, when pre-irradiated, increase stemness and survival of cocultured glioma cells. Tumor-naïve brains increased reactive astrocytes in response to radiation, and mice subjected to radiati
Objective: We evaluated whether patient-reported outcome trajectories (i.e., changes over time) differed by intraoperative compartmental cartilage lesion pattern over 4–6 years following arthroscopic meniscal surgery. Methods: In this ancillary study of the Knee Arthroscopy Cohort Southern Denmark cohort, we intraoperatively categorized cartilage lesions as isolated patellofemoral, isolated tibiof
Background: Despite intense research, the prognosis for patients with advanced colorectal cancer (CRC) remains poor. The prostaglandin D2 receptors DP1 and DP2 are explored here as potential therapeutic targets for advanced CRC. Methods: A CRC cohort was analysed to determine whether DP1 and DP2 receptor expression correlates with patient survival. Four colon cancer cell lines and a zebrafish meta
Background and aims: The precursor peptide of vasopressin, copeptin, has previously been linked to increased risk of developing diabetes mellitus, coronary artery disease and cardiovascular mortality. Whether elevated copeptin is associated with markers of atherosclerosis and arteriosclerosis in the general population is not known. Methods: In this population-based, cross-sectional study, coronary
Single-cell RNAseq is a routinely used method to explore heterogeneity within cell populations. Data from these experiments are often visualized using dimension reduction methods such as UMAP and tSNE, where each cell is projected in two or three dimensional space. Three-dimensional projections can be more informative for larger and complex datasets because they are less prone to merging and flatt
Production of red blood cells relies on proper mitochondrial function, both for their increased energy demands during differentiation and for proper heme and iron homeostasis. Mutations in genes regulating mitochondrial function have been reported in patients with anemia, yet their pathophysiological role often remains unclear. PGC1β is a critical coactivator of mitochondrial biogenesis, with incr
