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Doppler examination of the umbilical artery and the fetal middle cerebral artery is evaluated predominantly in pregnancies with fetuses in cephalic presentation and never has been elucidated in breech presentation. Evidence on the accuracy of fetal weight estimation in dependence of the fetal presentation is controversial. Nevertheless, clinical decisions including recommendations for a cesarean section or labor induction based on these examinations are applied to pregnancies with fetuses in breech presentation. The objective of this study was to investigate the influence of the fetal presentation on fetal weight estimation accuracy, umbilical artery and middle cerebral artery resistance indices (RI) in a prospective case control study. Ultrasound examinations in 305 uncomplicated term pregnancies (153 vertex presentations, 152 breech) were investigated. Non-parametric variables were compared using Pearson’s chi2 test and Wilcoxon chi2 test, depending on variable scaling. Fetal weight estimation accuracy was not significantly different between vertex presentation group (VP) (6.97%) and breech presentation group (BP) (7.96%, p = 0.099). Fetal head circumference measurements were significantly larger in BP (350 mm vs. 341 mm in VB, p > 0.0001) while abdominal circumferences were significantly smaller (VP: 338 mm, BP: 331 mm, p = 0.0039) and weight estimation was not significantly different. Umbilical artery RIs were not significantly different between VP (54.5) and BP (55.3, p = 0.354). Fetal middle cerebral artery RIs also showed no significant differences (VP: 71.2, BP: 70.7, p = 0.335). Our study shows that fetal Doppler (RI) and weight estimation ultrasound originally calibrated in cephalic pregnancies are applicable to pregnancies with fetuses in breech presentation.
s-processing in asymptotic giant branch stars in the light of revised neutron-capture cross sections
(2021)
Current AGB stellar models provide an adequate description of the s-process nucleosynthesis that occurs. Nonetheless, they still suffer from many uncertainties related to the modeling of the 13C pocket formation and the adopted nuclear reaction rates. For many important s-process isotopes, a best set of neutron-capture cross sections was recently re-evaluated. Using stellar models prescribing that the 13C pocket is a by-product of magnetic-buoyancy-induced mixing phenomena, s-process calculations were carried out with this database. Significant effects are found for a few s-only and branching point isotopes, pointing out the need for improved neutron-capture cross section measurements at low energy.
The activity of the Salt inducible kinase 2 (SIK2), a member of the AMP-activated protein kinase (AMPK)-related kinase family, has been linked to several biological processes that maintain cellular and energetic homeostasis. SIK2 is overexpressed in several cancers, including ovarian cancer, where it promotes the proliferation of metastases. Furthermore, as a centrosome kinase, SIK2 has been shown to regulate the G2/M transition, and its depletion sensitizes ovarian cancer to paclitaxel-based chemotherapy. Here, we report the consequences of SIK2 inhibition on mitosis and synergies with paclitaxel in ovarian cancer using a novel and selective inhibitor, MRIA9. We show that MRIA9-induced inhibition of SIK2 blocks the centrosome disjunction, impairs the centrosome alignment, and causes spindle mispositioning during mitosis. Furthermore, the inhibition of SIK2 using MRIA9 increases chromosomal instability, revealing the role of SIK2 in maintaining genomic stability. Finally, MRIA9 treatment enhances the sensitivity to paclitaxel in 3D-spheroids derived from ovarian cancer cell lines and ovarian cancer patients. Our study suggests selective targeting of SIK2 in ovarian cancer as a therapeutic strategy for overcoming paclitaxel resistance.
Glioblastoma (GBM) is the most common and most aggressive primary brain tumor, with a very high rate of recurrence and a median survival of 15 months after diagnosis. Abundant evidence suggests that a certain sub-population of cancer cells harbors a stem-like phenotype and is likely responsible for disease recurrence, treatment resistance and potentially even for the infiltrative growth of GBM. GBM incidence has been negatively correlated with the serum levels of 25-hydroxy-vitamin D3, while the low pH within tumors has been shown to promote the expression of the vitamin D3-degrading enzyme 24-hydroxylase, encoded by the CYP24A1 gene. Therefore, we hypothesized that calcitriol can specifically target stem-like glioblastoma cells and induce their differentiation. Here, we show, using in vitro limiting dilution assays, quantitative real-time PCR, quantitative proteomics and ex vivo adult organotypic brain slice transplantation cultures, that therapeutic doses of calcitriol, the hormonally active form of vitamin D3, reduce stemness to varying extents in a panel of investigated GSC lines, and that it effectively hinders tumor growth of responding GSCs ex vivo. We further show that calcitriol synergizes with Temozolomide ex vivo to completely eliminate some GSC tumors. These findings indicate that calcitriol carries potential as an adjuvant therapy for a subgroup of GBM patients and should be analyzed in more detail in follow-up studies.
Objective: We aimed to assess the correlation between serum prostate-specific antigen (PSA) and tumor burden in prostate cancer (PCa) patients undergoing radical prostatectomy (RP), because estimation of tumor burden is of high value, e.g., in men undergoing RP or with biochemical recurrence after RP. Patients and Methods: From January 2019 to June 2020, 179 consecutive PCa patients after RP with information on tumor and prostate weight were retrospectively identified from our prospective institutional RP database. Patients with preoperative systemic therapy (n=19), metastases (cM1, n=5), and locally progressed PCa (pT4 or pN1, n=50) were excluded from analyses. Histopathological features, including total weight of the prostate and specific tumor weight, were recorded by specialized uro-pathologists. Linear regression models were performed to evaluate the effect of PSA on tumor burden, measured by tumor weight after adjustment for patient and tumor characteristics. Results: Overall, median preoperative PSA was 7.0 ng/ml (interquartile range [IQR]: 5.41–10) and median age at surgery was 66 years (IQR: 61-71). Median prostate weight was 34 g (IQR: 26–46) and median tumor weight was 3.7 g (IQR: 1.8–7.1), respectively. In multivariable linear regression analysis after adjustment for patients and tumor characteristics, a significant, positive correlation could be detected between preoperative PSA and tumor weight (coefficient [coef.]: 0.37, CI: 0.15–0.6, p=0.001), indicating a robust increase in PSA of almost 0.4 ng/ml per 1g tumor weight. Conclusion: Preoperative PSA was significantly correlated with tumor weight in PCa patients undergoing RP, with an increase in PSA of almost 0.4 ng/ml per 1 g tumor weight. This might help to estimate both tumor burden before undergoing RP and in case of biochemical recurrence.
Artificial Intelligence (AI) has the potential to greatly improve the delivery of healthcare and other services that advance population health and wellbeing. However, the use of AI in healthcare also brings potential risks that may cause unintended harm. To guide future developments in AI, the High-Level Expert Group on AI set up by the European Commission (EC), recently published ethics guidelines for what it terms “trustworthy” AI. These guidelines are aimed at a variety of stakeholders, especially guiding practitioners toward more ethical and more robust applications of AI. In line with efforts of the EC, AI ethics scholarship focuses increasingly on converting abstract principles into actionable recommendations. However, the interpretation, relevance, and implementation of trustworthy AI depend on the domain and the context in which the AI system is used. The main contribution of this paper is to demonstrate how to use the general AI HLEG trustworthy AI guidelines in practice in the healthcare domain. To this end, we present a best practice of assessing the use of machine learning as a supportive tool to recognize cardiac arrest in emergency calls. The AI system under assessment is currently in use in the city of Copenhagen in Denmark. The assessment is accomplished by an independent team composed of philosophers, policy makers, social scientists, technical, legal, and medical experts. By leveraging an interdisciplinary team, we aim to expose the complex trade-offs and the necessity for such thorough human review when tackling socio-technical applications of AI in healthcare. For the assessment, we use a process to assess trustworthy AI, called 1Z-Inspection® to identify specific challenges and potential ethical trade-offs when we consider AI in practice.
Multinucleated giant cells (MNGCs) are frequently observed in the implantation areas of different biomaterials. The main aim of the present study was to analyze the long-term polarization pattern of the pro- and anti-inflammatory phenotypes of macrophages and MNGCs for 180 days to better understand their role in the success or failure of biomaterials. For this purpose, silk fibroin (SF) was implanted in a subcutaneous implantation model of Wistar rats as a model for biomaterial-induced MNGCs. A sham operation was used as a control for physiological wound healing. The expression of different inflammatory markers (proinflammatory M1: CCR-7, iNos; anti-inflammatory M2: CD-206, CD-163) and tartrate-resistant acid phosphatase (TRAP) and CD-68 were identified using immunohistochemical staining. The results showed significantly higher numbers of macrophages and MNGCs within the implantation bed of SF-expressed M1 markers, compared to M2 markers. Interestingly, the expression of proinflammatory markers was sustained over the long observation period of 180 days. By contrast, the control group showed a peak of M1 macrophages only on day 3. Thereafter, the inflammatory pattern shifted to M2 macrophages. No MNGCs were observed in the control group. To the best of our knowledge, this is study is the first to outline the persistence of pro-inflammatory MNGCs within the implantation bed of SF and to describe their long-term kinetics over 180 days. Clinically, these results are highly relevant to understand the role of biomaterial-induced MNGCs in the long term. These findings suggest that tailored physicochemical properties may be a key to avoiding extensive inflammatory reactions and achieving clinical success. Therefore, further research is needed to elucidate the correlation between proinflammatory MNGCs and the physicochemical characteristics of the implanted biomaterial.
Background and Aims. Systemic treatment with sorafenib has been the standard of care (SOC) in patients with advanced Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC) for more than a decade. TACE has been reported to allow better local tumor control in selected patients with BCLC stage C HCC. Methods. A retrospective analysis of patients with BCLC stage C HCC that were treated with sorafenib and TACE was conducted; they were compared to BCLC stage C patients treated either with TACE or sorafenib in the same period of time outside a clinical trial. Results. A total of 201 patients with BCLC stage C were identified, who were treated with either sorafenib and TACE (group A; n = 54), sorafenib (group B; n = 82) or TACE (group C; n = 65). No significant difference in baseline characteristics was observed. Time to progression was 7.0 months (95% CI: 4.3–9.7), 4.1 months (95% CI: 3.6–4.7) and 5.0 months (95% CI: 2.9–7.1) in groups A, B and C, respectively, and overall survival was 16.5 months (95% CI: 15.0–18.1), 8.4 months (95% CI: 6.0–10.8) and 10.5 months (95% CI: 7.5–13.6), respectively (group A vs. group B: p < 0.001; group A vs. group C: p = 0.0023). Adverse events of grade 3/4 occurred in 34% of patients in group A. Conclusions. Although sorafenib is a SOC in patients with BCLC stage C HCC, TACE is frequently used as an additional locoregional treatment in selected patients. This combined approach resulted in a significant overall survival benefit in selected patients, although randomized trials have not yet proven this benefit.
This paper addresses the development of performance-based assessment items for ICT skills, skills in dealing with information and communication technologies, a construct which is rather broadly and only operationally defined. Item development followed a construct-driven approach to ensure that test scores could be interpreted as intended. Specifically, ICT-specific knowledge as well as problem-solving and the comprehension of text and graphics were defined as components of ICT skills and cognitive ICT tasks (i.e., accessing, managing, integrating, evaluating, creating). In order to capture the construct in a valid way, design principles for constructing the simulation environment and response format were formulated. To empirically evaluate the very heterogeneous items and detect malfunctioning items, item difficulties were analyzed and behavior-related indicators with item-specific thresholds were developed and applied. The 69 item’s difficulty scores from the Rasch model fell within a comparable range for each cognitive task. Process indicators addressing time use and test-taker interactions were used to analyze whether most test-takers executed the intended processes, exhibited disengagement, or got lost among the items. Most items were capable of eliciting the intended behavior; for the few exceptions, conclusions for item revisions were drawn. The results affirm the utility of the proposed framework for developing and implementing performance-based items to assess ICT skills.
Responses of southern ocean seafloor habitats and communities to global and local drivers of change
(2021)
Knowledge of life on the Southern Ocean seafloor has substantially grown since the beginning of this century with increasing ship-based surveys and regular monitoring sites, new technologies and greatly enhanced data sharing. However, seafloor habitats and their communities exhibit high spatial variability and heterogeneity that challenges the way in which we assess the state of the Southern Ocean benthos on larger scales. The Antarctic shelf is rich in diversity compared with deeper water areas, important for storing carbon (“blue carbon”) and provides habitat for commercial fish species. In this paper, we focus on the seafloor habitats of the Antarctic shelf, which are vulnerable to drivers of change including increasing ocean temperatures, iceberg scour, sea ice melt, ocean acidification, fishing pressures, pollution and non-indigenous species. Some of the most vulnerable areas include the West Antarctic Peninsula, which is experiencing rapid regional warming and increased iceberg-scouring, subantarctic islands and tourist destinations where human activities and environmental conditions increase the potential for the establishment of non-indigenous species and active fishing areas around South Georgia, Heard and MacDonald Islands. Vulnerable species include those in areas of regional warming with low thermal tolerance, calcifying species susceptible to increasing ocean acidity as well as slow-growing habitat-forming species that can be damaged by fishing gears e.g., sponges, bryozoan, and coral species. Management regimes can protect seafloor habitats and key species from fishing activities; some areas will need more protection than others, accounting for specific traits that make species vulnerable, slow growing and long-lived species, restricted locations with optimum physiological conditions and available food, and restricted distributions of rare species. Ecosystem-based management practices and long-term, highly protected areas may be the most effective tools in the preservation of vulnerable seafloor habitats. Here, we focus on outlining seafloor responses to drivers of change observed to date and projections for the future. We discuss the need for action to preserve seafloor habitats under climate change, fishing pressures and other anthropogenic impacts.