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  • 1
    In: Journal of Instrumentation, IOP Publishing, Vol. 17, No. 01 ( 2022-01-01), p. P01013-
    Abstract: The semiconductor tracker (SCT) is one of the tracking systems for charged particles in the ATLAS detector. It consists of 4088 silicon strip sensor modules. During Run 2 (2015–2018) the Large Hadron Collider delivered an integrated luminosity of 156 fb -1 to the ATLAS experiment at a centre-of-mass proton-proton collision energy of 13 TeV. The instantaneous luminosity and pile-up conditions were far in excess of those assumed in the original design of the SCT detector. Due to improvements to the data acquisition system, the SCT operated stably throughout Run 2. It was available for 99.9% of the integrated luminosity and achieved a data-quality efficiency of 99.85%. Detailed studies have been made of the leakage current in SCT modules and the evolution of the full depletion voltage, which are used to study the impact of radiation damage to the modules.
    Type of Medium: Online Resource
    ISSN: 1748-0221
    Language: Unknown
    Publisher: IOP Publishing
    Publication Date: 2022
    detail.hit.zdb_id: 2235672-1
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  • 2
    In: Frontiers in Bioengineering and Biotechnology, Frontiers Media SA, Vol. 9 ( 2021-6-17)
    Abstract: Functioning as the outermost self-renewing protective layer of the human organism, skin protects against a multitude of harmful biological and physical stimuli. Consisting of ectodermal, mesenchymal, and neural crest-derived cell lineages, tissue homeostasis, and signal transduction are finely tuned through the interplay of various pathways. A health problem of astronauts in space is skin deterioration. Until today, wound healing has not been considered as a severe health concern for crew members. This can change with deep space exploration missions and commercial spaceflights together with space tourism. Albeit the molecular process of wound healing is not fully elucidated yet, there have been established significant conceptual gains and new scientific methods. Apoptosis, e.g., programmed cell death, enables orchestrated development and cell removal in wounded or infected tissue. Experimental designs utilizing microgravity allow new insights into the role of apoptosis in wound healing. Furthermore, impaired wound healing in unloading conditions would depict a significant challenge in human-crewed exploration space missions. In this review, we provide an overview of alterations in the behavior of cutaneous cell lineages under microgravity in regard to the impact of apoptosis in wound healing. We discuss the current knowledge about wound healing in space and simulated microgravity with respect to apoptosis and available therapeutic strategies.
    Type of Medium: Online Resource
    ISSN: 2296-4185
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2719493-0
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  • 3
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 2 ( 2023-01-07), p. 1181-
    Abstract: Microgravity changes the gene expression pattern in various cell types. This study focuses on the breast cancer cell lines MCF-7 (less invasive) and MDA-MB-231 (triple-negative, highly invasive). The cells were cultured for 14 days under simulated microgravity (s-µg) conditions using a random positioning machine (RPM). We investigated cytoskeletal and extracellular matrix (ECM) factors as well as focal adhesion (FA) and the transmembrane proteins involved in different cellular signaling pathways (MAPK, PAM and VEGF). The mRNA expressions of 24 genes of interest (TUBB, ACTB, COL1A1, COL4A5, LAMA3, ITGB1, CD44, VEGF, FLK1, EGFR, SRC, FAK1, RAF1, AKT1, ERK1, MAPK14, MAP2K1, MTOR, RICTOR, VCL, PXN, CDKN1, CTNNA1 and CTNNB1) were determined by quantitative real-time PCR (qPCR) and studied using STRING interaction analysis. Histochemical staining was carried out to investigate the morphology of the adherent cells (ADs) and the multicellular spheroids (MCSs) after RPM exposure. To better understand this experimental model in the context of breast cancer patients, a weighted gene co-expression network analysis (WGCNA) was conducted to obtain the expression profiles of 35 breast cell lines from the HMS LINCS Database. The qPCR-verified genes were searched in the mammalian phenotype database and the human genome-wide association studies (GWAS) Catalog. The results demonstrated the positive association between the real metastatic microtumor environment and MCSs with respect to the extracellular matrix, cytoskeleton, morphology, different cellular signaling pathway key proteins and several other components. In summary, the microgravity-engineered three-dimensional MCS model can be utilized to study breast cancer cell behavior and to assess the therapeutic efficacies of drugs against breast cancer in the future.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 4
    In: JAMA, American Medical Association (AMA), Vol. 329, No. 14 ( 2023-04-11), p. 1183-
    Abstract: Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02735707
    Type of Medium: Online Resource
    ISSN: 0098-7484
    RVK:
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
    detail.hit.zdb_id: 2958-0
    detail.hit.zdb_id: 2018410-4
    SSG: 5,21
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  • 5
    In: JAMA, American Medical Association (AMA), Vol. 329, No. 1 ( 2023-01-03), p. 39-
    Abstract: The longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown. Objective To determine the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes. Design, Setting, and Participants Prespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains in which 4869 critically ill adult patients with COVID-19 were enrolled between March 9, 2020, and June 22, 2021, from 197 sites in 14 countries. The final 180-day follow-up was completed on March 2, 2022. Interventions Patients were randomized to receive 1 or more interventions within 6 treatment domains: immune modulators (n = 2274), convalescent plasma (n = 2011), antiplatelet therapy (n = 1557), anticoagulation (n = 1033), antivirals (n = 726), and corticosteroids (n = 401). Main Outcomes and Measures The main outcome was survival through day 180, analyzed using a bayesian piecewise exponential model. A hazard ratio (HR) less than 1 represented improved survival (superiority), while an HR greater than 1 represented worsened survival (harm); futility was represented by a relative improvement less than 20% in outcome, shown by an HR greater than 0.83. Results Among 4869 randomized patients (mean age, 59.3 years; 1537 [32.1%] women), 4107 (84.3%) had known vital status and 2590 (63.1%) were alive at day 180. IL-6 receptor antagonists had a greater than 99.9% probability of improving 6-month survival (adjusted HR, 0.74 [95% credible interval {CrI}, 0.61-0.90] ) and antiplatelet agents had a 95% probability of improving 6-month survival (adjusted HR, 0.85 [95% CrI, 0.71-1.03]) compared with the control, while the probability of trial-defined statistical futility (HR & amp;gt;0.83) was high for therapeutic anticoagulation (99.9%; HR, 1.13 [95% CrI, 0.93-1.42]), convalescent plasma (99.2%; HR, 0.99 [95% CrI, 0.86-1.14] ), and lopinavir-ritonavir (96.6%; HR, 1.06 [95% CrI, 0.82-1.38]) and the probabilities of harm from hydroxychloroquine (96.9%; HR, 1.51 [95% CrI, 0.98-2.29] ) and the combination of lopinavir-ritonavir and hydroxychloroquine (96.8%; HR, 1.61 [95% CrI, 0.97-2.67]) were high. The corticosteroid domain was stopped early prior to reaching a predefined statistical trigger; there was a 57.1% to 61.6% probability of improving 6-month surviva l across varying hydrocortisone dosing strategies. Conclusions and Relevance Among critically ill patients with COVID-19 randomized to receive 1 or more therapeutic interventions, treatment with an IL-6 receptor antagonist had a greater than 99.9% probability of improved 180-day mortality compared with patients randomized to the control, and treatment with an antiplatelet had a 95.0% probability of improved 180-day mortality compared with patients randomized to the control. Overall, when considered with previously reported short-term results, the findings indicate that initial in-hospital treatment effects were consistent for most therapies through 6 months.
    Type of Medium: Online Resource
    ISSN: 0098-7484
    RVK:
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
    detail.hit.zdb_id: 2958-0
    detail.hit.zdb_id: 2018410-4
    SSG: 5,21
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  • 6
    In: JAMA, American Medical Association (AMA), Vol. 327, No. 13 ( 2022-04-05), p. 1247-
    Type of Medium: Online Resource
    ISSN: 0098-7484
    RVK:
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2022
    detail.hit.zdb_id: 2958-0
    detail.hit.zdb_id: 2018410-4
    SSG: 5,21
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  • 7
    In: Intensive Care Medicine, Springer Science and Business Media LLC, Vol. 47, No. 8 ( 2021-08), p. 867-886
    Type of Medium: Online Resource
    ISSN: 0342-4642 , 1432-1238
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 1459201-0
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  • 8
    In: Cancers, MDPI AG, Vol. 15, No. 6 ( 2023-03-07), p. 1641-
    Abstract: We recently reported that synthetic glucocorticoid dexamethasone (DEX) is able to suppress metastasis-like spheroid formation in a culture of follicular thyroid cancer (FTC)-133 cells cultured under random positioning. We now show that this inhibition was selective for two metastatic thyroid carcinoma cells, FTC-133 and WRO, whereas benign Nthy-ori 3-1 thyrocytes and recurrent ML-1 follicular thyroid cancer cells were not affected by DEX. We then compare Nthy-ori 3-1 and FTC-133 cells concerning their adhesion and mechanosignaling. We demonstrate that DEX disrupts random positioning-triggered p38 stress signaling in FTC-133 cells, thereby antagonizing a variety of biological functions. Thus, DEX treatment of FTC-133 cells is associated with increased adhesiveness, which is mainly caused by the restored, pronounced formation of a normal number of tight junctions. Moreover, we show that Nthy-ori 3-1 and ML-1 cells upregulate the anti-adhesion protein mucin-1 during random positioning, presumably as a protection against mechanical stress. In summary, mechanical stress seems to be an important component in this metastasis model system that is processed differently by metastatic and healthy cells. The balance between adhesion, anti-adhesion and cell–cell connections enables detachment of adherent human cells on the random positioning machine—or not, allowing selective inhibition of thyroid in vitro metastasis by DEX.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527080-1
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  • 9
    In: Alzheimer's Research & Therapy, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2021-03-25)
    Abstract: To explore the utility of the International Working Group (IWG)-1 criteria in recruitment for Alzheimer’s disease (AD) clinical trials, we applied the more recently proposed research diagnostic criteria to individuals enrolled in a randomized controlled prevention trial (RCT) and assessed their disease progression. Methods The multinational LipiDiDiet RCT targeted 311 individuals with IWG-1 defined prodromal AD. Based on centrally analyzed baseline biomarkers, participants were classified according to the IWG-2 and National Institute on Aging–Alzheimer’s Association (NIA-AA) 2011 and 2018 criteria. Linear mixed models were used to investigate the 2-year change in cognitive and functional performance (Neuropsychological Test Battery NTB Z scores, Clinical Dementia Rating-Sum of Boxes CDR-SB) (criteria × time interactions; baseline score, randomization group, sex, Mini-Mental State Examination (MMSE), and age also included in the models). Cox models adjusted for randomization group, MMSE, sex, age, and study site were used to investigate the risk of progression to dementia over 2 years. Results In total, 88%, 86%, and 69% of participants had abnormal cerebrospinal fluid (CSF) β-amyloid, total tau, and phosphorylated tau, respectively; 64% had an A+T+N+ profile (CSF available for N  = 107). Cognitive-functional decline appeared to be more pronounced in the IWG-2 prodromal AD, NIA-AA 2011 high and intermediate AD likelihood, and NIA-AA 2018 AD groups, but few significant differences were observed between the groups within each set of criteria. Hazard ratio (95% CI) for dementia was 4.6 (1.6–13.7) for IWG-2 prodromal AD (reference group no prodromal AD), 7.4 (1.0–54.7) for NIA-AA 2011 high AD likelihood (reference group suspected non-AD pathology SNAP), and 9.4 (1.2–72.7) for NIA-AA 2018 AD (reference group non-Alzheimer’s pathologic change). Compared with the NIA-AA 2011 high AD likelihood group (abnormal β-amyloid and neuronal injury markers), disease progression was similar in the intermediate AD likelihood group (medial temporal lobe atrophy; no CSF available). Conclusions Despite being less restrictive than the other criteria, the IWG-1 criteria reliably identified individuals with AD pathology. More pragmatic and easily applicable selection criteria might be preferred due to feasibility in certain situations, e.g., in multidomain prevention trials that do not specifically target β-amyloid/tau pathologies. Trial registration Netherlands Trial Register, NL1620 . Registered on 9 March 2009
    Type of Medium: Online Resource
    ISSN: 1758-9193
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2506521-X
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  • 10
    In: npj Microgravity, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2024-02-10)
    Abstract: Progress in mechanobiology allowed us to better understand the important role of mechanical forces in the regulation of biological processes. Space research in the field of life sciences clearly showed that gravity plays a crucial role in biological processes. The space environment offers the unique opportunity to carry out experiments without gravity, helping us not only to understand the effects of gravitational alterations on biological systems but also the mechanisms underlying mechanoperception and cell/tissue response to mechanical and gravitational stresses. Despite the progress made so far, for future space exploration programs it is necessary to increase our knowledge on the mechanotransduction processes as well as on the molecular mechanisms underlying microgravity-induced cell and tissue alterations. This white paper reports the suggestions and recommendations of the SciSpacE Science Community for the elaboration of the section of the European Space Agency roadmap “Biology in Space and Analogue Environments” focusing on “How are cells and tissues influenced by gravity and what are the gravity perception mechanisms?” The knowledge gaps that prevent the Science Community from fully answering this question and the activities proposed to fill them are discussed.
    Type of Medium: Online Resource
    ISSN: 2373-8065
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2024
    detail.hit.zdb_id: 2823626-9
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