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Aims: The high mortality in untreated acute type A aortic dissection (ATAAD) stresses the need for prompt diagnosis and immediate surgical treatment. Our aim was to evaluate the frequency and clinical impact of misdiagnosis and delayed diagnosis of ATAAD. Methods and results: This was a single-centre, retrospective, observational study including all ATAAD patients with available admission charts b
α-Synuclein is a synaptic protein that accumulates primarily in synucleinopathies and secondarily in certain lysosomal storage disorders. However, its physiological roles in health and disease are not fully understood. In part, this has been hampered by the inability to visualize α-synuclein and its cellular localization, due to the lack of specific antibodies and faithful reporters. Here, we used
Glial fibrillary acidic protein (GFAP) is a type-3 intermediate filament protein mainly expressed in astrocytes in the central nervous system. Mutations in GFAP cause Alexander disease (AxD), a rare and fatal neurological disorder. How exactly mutant GFAP eventually leads to white and gray matter deterioration in AxD remains unknown. GFAP is known to be expressed also in neural precursor cells in
Approaches to differentiating pluripotent stem cells (PSCs) into neurons currently face two major challenges-(i) generated cells are immature, with limited functional properties; and (ii) cultures exhibit heterogeneous neuronal subtypes and maturation stages. Using lineage-determining transcription factors, we previously developed a single-step method to generate glutamatergic neurons from human P
We and others have shown that embryonic and neonatal fibroblasts can be directly converted into induced neuronal (iN) cells with mature functional properties. Reprogramming of fibroblasts from adult and aged mice, however, has not yet been explored in detail. The ability to generate fully functional iN cells from aged organisms will be particularly important for in vitro modeling of diseases of ol
We recently showed that defined sets of transcription factors are sufficient to convert mouse and human fibroblasts directly into cells resembling functional neurons, referred to as "induced neuronal"(iN) cells. For some applications however, it would be desirable to convert fibroblasts into proliferative neural precursor cells (NPCs) instead of neurons. We hypothesized that NPC-like cells may be
Available methods for differentiating human embryonic stem cells (ESCs) and induced pluripotent cells (iPSCs) into neurons are often cumbersome, slow, and variable. Alternatively, human fibroblasts can be directly converted into induced neuronal (iN) cells. However, with present techniques conversion is inefficient, synapse formation is limited, and only small amounts of neurons can be generated.
Transplantation of oligodendrocyte precursor cells (OPCs) is a promising potential therapeutic strategy for diseases affecting myelin. However, the derivation of engraftable OPCs from human pluripotent stem cells has proven difficult and primary OPCs are not readily available. Here we report the generation of induced OPCs (iOPCs) by direct lineage conversion. Forced expression of the three transcr
Direct conversion of nonneural cells to functional neurons holds great promise for neurological disease modeling and regenerative medicine. We previously reported rapid reprogramming of mouse embryonic fibroblasts (MEFs) into mature induced neuronal (iN) cells by forced expression of three transcription factors: ASCL1, MYT1L, and BRN2. Here, we show that ASCL1 alone is sufficient to generate funct
Artificial Intelligence methods are powerful tools for biological image analysis and processing. High-quality annotated images are key to training and developing new methods, but access to such data is often hindered by the lack of standards for sharing datasets. We brought together community experts in a workshop to develop guidelines to improve the reuse of bioimages and annotations for AI appli
Functionalized computed tomography (CT) in combination with labelled cells is virtually non-existent due to the limited sensitivity of X-ray-absorption-based imaging, but would be highly desirable to realise cell tracking studies in entire organisms. In this study we applied in-line free propagation X-ray phase-contrast CT (XPCT) in an allergic asthma mouse model to assess structural changes as we
One of the key purposes of bone tissue engineering is the development of new biomaterials that can stimulate the body's own regenerative mechanism for patient's anatomical and functional recovery. Bioactive glasses, due to their versatile properties, are excellent candidates to fabricate porous 3-D architectures for bone replacement. In this work, morphological and structural investigations are ca
The small size of the adult and developing mouse heart poses a great challenge for imaging in preclinical research. The aim of the study was to establish a phosphotungstic acid (PTA) ex-vivo staining approach that efficiently enhances the x-ray attenuation of soft-tissue to allow high resolution 3D visualization of mouse hearts by synchrotron radiation based μCT (SRμCT) and classical μCT. We demon
Background: In recent years, there has been interest on the fabrication of systems using particulates or block-based approach for bone tissue engineering (TE) scaffolds, possessing porous interconnected structures. In fact, these particular morphologies greatly increase the surface area for more chemical and biological reactions to take place. Purpose: This study was designed to demonstrate the un
In mice, along with the assessment of eosinophils, lung function measurements, most commonly carried out by plethysmography, are essential to monitor the course of allergic airway inflammation, to examine therapy efficacy and to correlate animal with patient data. To date, plethysmography techniques either use intubation and/or restraining of the mice and are thus invasive, or are limited in their
When attempting to establish accurate models for the human diploe, micro-scale morphological differences in the four main areas of the calvaria could also be considered. In this study, X-ray computed microtomography (μ-CT) images were analyzed in order to quantitatively characterize the micro-architecture of the human calvarium diploe. A bone specimen from each area of the skull (temporal, frontal
Lung imaging in mouse disease models is crucial for the assessment of the severity of airway disease but remains challenging due to the small size and the high porosity of the organ. Synchrotron inline free-propagation phase-contrast computed tomography (CT) with its intrinsic high soft-tissue contrast provides the necessary sensitivity and spatial resolution to analyse the mouse lung structure in
Propagation-based X-ray phase-contrast computed tomography (PBI) has already proven its potential in a great variety of soft-tissue-related applications including lung imaging. However, the strong edge enhancement, caused by the phase effects, often hampers image segmentation and therefore the quantitative analysis of data sets. Here, the benefits of applying single-distance phase retrieval prior
Background/Objectives: There is still no consensus as to whether patients with upfront resectable synchronous colorectal liver metastases (sCRLM) should receive neoadjuvant treatment prior to liver surgery. Two randomized controlled trials have assessed the role of peri-operative chemotherapy in sCRLM; neither have shown a survival benefit in the neoadjuvant group. The aim of this population-based
