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  • 1
    Online Resource
    Online Resource
    A second update on mapping the human genetic architecture of COVID-19
    Springer Science and Business Media LLC ; 2023
    In:  Nature Vol. 621, No. 7977 ( 2023-09-07), p. E7-E26
    Details
    In: Nature, Springer Science and Business Media LLC, Vol. 621, No. 7977 ( 2023-09-07), p. E7-E26
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
    URL: Article
    DOI: 10.1038/s41586-023-06355-3
    RVK:
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    RVK:
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    RVK:
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
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  • 2
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    Endovascular thrombectomy for acute ischaemic stroke with established large infarct: multicentre, open-label, randomised trial
    Elsevier BV ; 2023
    In:  The Lancet Vol. 402, No. 10414 ( 2023-11), p. 1753-1763
    Details
    In: The Lancet, Elsevier BV, Vol. 402, No. 10414 ( 2023-11), p. 1753-1763
    Type of Medium: Online Resource
    ISSN: 0140-6736
    URL: Article
    DOI: 10.1016/S0140-6736(23)02032-9
    RVK:
    XA 10000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
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  • 3
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    Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals
    Springer Science and Business Media LLC ; 2023
    In:  Nature Communications Vol. 14, No. 1 ( 2023-07-20)
    Details
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 14, No. 1 ( 2023-07-20)
    Abstract: Copy number variants (CNV) are established risk factors for neurodevelopmental disorders with seizures or epilepsy. With the hypothesis that seizure disorders share genetic risk factors, we pooled CNV data from 10,590 individuals with seizure disorders, 16,109 individuals with clinically validated epilepsy, and 492,324 population controls and identified 25 genome-wide significant loci, 22 of which are novel for seizure disorders, such as deletions at 1p36.33, 1q44, 2p21-p16.3, 3q29, 8p23.3-p23.2, 9p24.3, 10q26.3, 15q11.2, 15q12-q13.1, 16p12.2, 17q21.31, duplications at 2q13, 9q34.3, 16p13.3, 17q12, 19p13.3, 20q13.33, and reciprocal CNVs at 16p11.2, and 22q11.21. Using genetic data from additional 248,751 individuals with 23 neuropsychiatric phenotypes, we explored the pleiotropy of these 25 loci. Finally, in a subset of individuals with epilepsy and detailed clinical data available, we performed phenome-wide association analyses between individual CNVs and clinical annotations categorized through the Human Phenotype Ontology (HPO). For six CNVs, we identified 19 significant associations with specific HPO terms and generated, for all CNVs, phenotype signatures across 17 clinical categories relevant for epileptologists. This is the most comprehensive investigation of CNVs in epilepsy and related seizure disorders, with potential implications for clinical practice.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    URL: Article
    DOI: 10.1038/s41467-023-39539-6
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
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  • 4
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    Zinc-Doped Bioactive Glass/Polycaprolactone Hybrid Scaffolds Manufactured by Direct and Indirect 3D Printing Methods for Bone Regeneration
    MDPI AG ; 2023
    In:  Cells Vol. 12, No. 13 ( 2023-06-30), p. 1759-
    Details
    In: Cells, MDPI AG, Vol. 12, No. 13 ( 2023-06-30), p. 1759-
    Abstract: A novel organic–inorganic hybrid, based on SiO2-CaO-ZnO bioactive glass (BG) and polycaprolactone (PCL), associating the highly bioactive and versatile bioactive glass with clinically established PCL was examined. The BG–PCL hybrid is obtained by acid-catalyzed silica sol–gel process inside PCL solution either by direct or indirect printing. Apatite-formation tests in simulated body fluid (SBF) confirm the ion release along with the hybrid’s bone-like apatite forming. Kinetics differ significantly between directly and indirectly printed scaffolds, the former requiring longer periods to degrade, while the latter demonstrates faster calcium phosphate (CaP) formation. Remarkably, Zn diffusion and accumulation are observed at the surface within the newly formed active CaP layer. Zn release is found to be dependent on printing method and immersion medium. Investigation of BG at the atomic scale reveals the ambivalent role of Zn, capable of acting both as a network modifier and as a network former linking the BG silicate network. In addition, hMSCs viability assay proves no cytotoxicity of the Zn hybrid. LIVE/DEAD staining demonstrated excellent cell viability and proliferation for over seven weeks. Overall, this hybrid material either non-doped or doped with a metal trace element is a promising candidate to be translated to clinical applications for bone regeneration.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells12131759
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
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  • 5
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    Impact of Tranexamic Acid on Chondrocytes and Osteogenically Differentiated Human Mesenchymal Stromal Cells (hMSCs) In Vitro
    MDPI AG ; 2020
    In:  Journal of Clinical Medicine Vol. 9, No. 12 ( 2020-11-29), p. 3880-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 9, No. 12 ( 2020-11-29), p. 3880-
    Abstract: The topical application of tranexamic acid (TXA) helps to prevent post-operative blood loss in total joint replacements. Despite these findings, the effects on articular and periarticular tissues remain unclear. Therefore, this in vitro study examined the effects of varying exposure times and concentrations of TXA on proliferation rates, gene expression and differentiation capacity of chondrocytes and human mesenchymal stromal cells (hMSCs), which underwent osteogenic differentiation. Chondrocytes and hMSCs were isolated and multiplied in monolayer cell cultures. Osteogenic differentiation of hMSCs was induced for 21 days using a differentiation medium containing specific growth factors. Cell proliferation was analyzed using ATP assays. Effects of TXA on cell morphology were examined via light microscopy and histological staining, while expression levels of tissue-specific genes were measured using semiquantitative RT-PCR. After treatment with 50 mg/mL of TXA, a decrease in cell proliferation rates was observed. Furthermore, treatment with concentrations of 20 mg/mL of TXA for at least 48 h led to a visible detachment of chondrocytes. TXA treatment with 50 mg/mL for at least 24 h led to a decrease in the expression of specific marker genes in chondrocytes and osteogenically differentiated hMSCs. No significant effects were observed for concentrations beyond 20 mg/mL of TXA combined with exposure times of less than 24 h. This might therefore represent a safe limit for topical application in vivo. Further research regarding in vivo conditions and effects on hMSC functionality are necessary to fully determine the effects of TXA on articular and periarticular tissues.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm9123880
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
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  • 6
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    Combinations of Hydrogels and Mesenchymal Stromal Cells (MSCs) for Cartilage Tissue Engineering—A Review of the Literature
    MDPI AG ; 2021
    In:  Gels Vol. 7, No. 4 ( 2021-11-16), p. 217-
    Details
    In: Gels, MDPI AG, Vol. 7, No. 4 ( 2021-11-16), p. 217-
    Abstract: Cartilage offers limited regenerative capacity. Cell-based approaches have emerged as a promising alternative in the treatment of cartilage defects and osteoarthritis. Due to their easy accessibility, abundancy, and chondrogenic potential mesenchymal stromal cells (MSCs) offer an attractive cell source. MSCs are often combined with natural or synthetic hydrogels providing tunable biocompatibility, biodegradability, and enhanced cell functionality. In this review, we focused on the different advantages and disadvantages of various natural, synthetic, and modified hydrogels. We examined the different combinations of MSC-subpopulations and hydrogels used for cartilage engineering in preclinical and clinical studies and reviewed the effects of added growth factors or gene transfer on chondrogenesis in MSC-laden hydrogels. The aim of this review is to add to the understanding of the disadvantages and advantages of various combinations of MSC-subpopulations, growth factors, gene transfers, and hydrogels in cartilage engineering.
    Type of Medium: Online Resource
    ISSN: 2310-2861
    URL: Article
    DOI: 10.3390/gels7040217
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
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  • 7
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    Fibroblast-like cells change gene expression of bone remodelling markers in transwell cultures
    Springer Science and Business Media LLC ; 2020
    In:  European Journal of Medical Research Vol. 25, No. 1 ( 2020-12)
    Details
    In: European Journal of Medical Research, Springer Science and Business Media LLC, Vol. 25, No. 1 ( 2020-12)
    Abstract: Periprosthetic fibroblast-like cells (PPFs) play an important role in aseptic loosening of arthroplasties. Various studies have examined PPF behavior in monolayer culture systems. However, the periprosthetic tissue is a three-dimensional (3D) mesh, which allows the cells to interact in a multidirectional way. The expression of bone remodeling markers of fibroblast-like cells in a multilayer environment changes significantly versus monolayer cultures without the addition of particles or cytokine stimulation. Gene expression of bone remodeling markers was therefore compared in fibroblast-like cells from different origins and dermal fibroblasts under transwell culture conditions versus monolayer cultures. Methods PPFs from periprosthetic tissues ( n  = 12), osteoarthritic (OA) synovial fibroblast-like cells (SFs) ( n  = 6), and dermal fibroblasts (DFs) were cultured in monolayer (density 5.5 × 10 3 /cm 2 ) or multilayer cultures (density 8.5 × 10 5 /cm 2 ) for 10 or 21 days. Cultures were examined via histology, TRAP staining, immunohistochemistry (anti-S100a4), and quantitative real-time PCR. Results Fibroblast-like cells (PPFs/SFs) and dermal fibroblasts significantly increased the expression of RANKL and significantly decreased the expression of ALP, COL1A1, and OPG in multilayer cultures. PPFs and SFs in multilayer cultures further showed a higher expression of cathepsin K, MMP-13, and TNF-α. In multilayer PPF cultures, the mRNA level of TRAP was also found to be significantly increased. Conclusion The multilayer cultures are able to induce significant expression changes in fibroblast-like cells depending on the nature of cellular origin without the addition of any further stimulus. This system might be a useful tool to get more in vivo like results regarding fibroblast-like cell cultures.
    Type of Medium: Online Resource
    ISSN: 2047-783X
    URL: Article
    DOI: 10.1186/s40001-020-00453-y
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
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  • 8
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    Mesenchymal Stromal Cells (MSCs) Isolated from Various Tissues of the Human Arthritic Knee Joint Possess Similar Multipotent Differentiation Potential
    MDPI AG ; 2022
    In:  Applied Sciences Vol. 12, No. 4 ( 2022-02-21), p. 2239-
    Details
    In: Applied Sciences, MDPI AG, Vol. 12, No. 4 ( 2022-02-21), p. 2239-
    Abstract: (1) Background: The mesenchymal stromal cells (MSCs) of different tissue origins are applied in cell-based chondrogenic regeneration. However, there is a lack of comparability determining the most suitable cell source for the tissue engineering (TE) of cartilage. The purpose of this study was to compare the in vitro chondrogenic potential of MSC-like cells from different tissue sources (bone marrow, meniscus, anterior cruciate ligament, synovial membrane, and the infrapatellar fat pad removed during total knee arthroplasty (TKA)) and define which cell source is best suited for cartilage regeneration. (2) Methods: MSC-like cells were isolated from five donors and expanded using adherent monolayer cultures. Differentiation was induced by culture media containing specific growth factors. Transforming growth factor (TGF)-ß1 was used as the growth factor for chondrogenic differentiation. Osteogenesis and adipogenesis were induced in monolayer cultures for 27 days, while pellet cell cultures were used for chondrogenesis for 21 days. Control cultures were maintained under the same conditions. After, the differentiation period samples were analyzed, using histological and immunohistochemical staining, as well as molecularbiological analysis by RT-PCR, to assess the expression of specific marker genes. (3) Results: Plastic-adherent growth and in vitro trilineage differentiation capacity of all isolated cells were proven. Flow cytometry revealed the clear co-expression of surface markers CD44, CD73, CD90, and CD105 on all isolated cells. Adipogenesis was validated through the formation of lipid droplets, while osteogenesis was proven by the formation of calcium deposits within differentiated cell cultures. The formation of proteoglycans was observed during chondrogenesis in pellet cultures, with immunohistochemical staining revealing an increased relative gene expression of collagen type II. RT-PCR proved an elevated expression of specific marker genes after successful differentiation, with no significant differences regarding different cell source of native tissue. (4) Conclusions: Irrespective of the cell source of native tissue, all MSC-like cells showed multipotent differentiation potential in vitro. The multipotent differentiation capacity did not differ significantly, and chondrogenic differentiation was proven in all pellet cultures. Therefore, cell suitability for cell-based cartilage therapies and tissue engineering is given for various tissue origins that are routinely removed during total knee arthroplasty (TKA). This study might provide essential information for the clinical tool of cell harvesting, leading to more flexibility in cell availability.
    Type of Medium: Online Resource
    ISSN: 2076-3417
    URL: Article
    DOI: 10.3390/app12042239
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
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  • 9
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    Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection
    American Medical Association (AMA) ; 2023
    In:  JAMA Vol. 329, No. 22 ( 2023-06-13), p. 1934-
    Details
    In: JAMA, American Medical Association (AMA), Vol. 329, No. 22 ( 2023-06-13), p. 1934-
    Abstract: SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID . Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals. Objective To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections. Design, Setting, and Participants Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling. Exposure SARS-CoV-2 infection. Main Outcomes and Measures PASC and 44 participant-reported symptoms (with severity thresholds). Results A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%] ) were PASC positive at 6 months. Conclusions and Relevance A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.
    Type of Medium: Online Resource
    ISSN: 0098-7484
    URL: Article
    DOI: 10.1001/jama.2023.8823
    RVK:
    XA 10000
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
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  • 10
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    EUREC〈sup〉4〈/sup〉A
    Copernicus GmbH ; 2021
    In:  Earth System Science Data Vol. 13, No. 8 ( 2021-08-25), p. 4067-4119
    Details
    In: Earth System Science Data, Copernicus GmbH, Vol. 13, No. 8 ( 2021-08-25), p. 4067-4119
    Abstract: Abstract. The science guiding the EUREC4A campaign and its measurements is presented. EUREC4A comprised roughly 5 weeks of measurements in the downstream winter trades of the North Atlantic – eastward and southeastward of Barbados. Through its ability to characterize processes operating across a wide range of scales, EUREC4A marked a turning point in our ability to observationally study factors influencing clouds in the trades, how they will respond to warming, and their link to other components of the earth system, such as upper-ocean processes or the life cycle of particulate matter. This characterization was made possible by thousands (2500) of sondes distributed to measure circulations on meso- (200 km) and larger (500 km) scales, roughly 400 h of flight time by four heavily instrumented research aircraft; four global-class research vessels; an advanced ground-based cloud observatory; scores of autonomous observing platforms operating in the upper ocean (nearly 10 000 profiles), lower atmosphere (continuous profiling), and along the air–sea interface; a network of water stable isotopologue measurements; targeted tasking of satellite remote sensing; and modeling with a new generation of weather and climate models. In addition to providing an outline of the novel measurements and their composition into a unified and coordinated campaign, the six distinct scientific facets that EUREC4A explored – from North Brazil Current rings to turbulence-induced clustering of cloud droplets and its influence on warm-rain formation – are presented along with an overview of EUREC4A's outreach activities, environmental impact, and guidelines for scientific practice. Track data for all platforms are standardized and accessible at https://doi.org/10.25326/165 (Stevens, 2021), and a film documenting the campaign is provided as a video supplement.
    Type of Medium: Online Resource
    ISSN: 1866-3516
    URL: Article
    DOI: 10.5194/essd-13-4067-2021
    Language: English
    Publisher: Copernicus GmbH
    Publication Date: 2021
    detail.hit.zdb_id: 2475469-9
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