Abstract Context Measurement of plasma steroids is necessary for diagnosis of congenital adrenal hyperplasia (CAH). We sought to establish an efficient strategy for detection and subtyping of CAH with a machine-learning algorithm. Methods Clinical phenotype and genetic testing were used to provide CAH diagnosis and subtype. We profiled 13 major steroid hormones by liquid chromatography-tandem mass spectrometry. A multiclassifier system was established to distinguish 11β-hydroxylase deficiency (11βOHD), 17α-hydroxylase/17,20-lyase deficiency (17OHD), and 21α-hydroxylase deficiency (21OHD) in a discovery cohort (n = 226). It was then validated in an independent cohort (n = 111) and finally applied in a perspective cohort of 256 patients. The diagnostic performance on the basis of area under receiver operating characteristic curves (AUCs) was evaluated. Results A cascade logistic regression model, we named the “Steroidogenesis Score”, was able to discriminate the 3 most common CAH subtypes: 11βOHD, 17OHD, and 21OHD. In the perspective application cohort, the steroidogenesis score had a high diagnostic accuracy for all 3 subtypes, 11βOHD (AUC, 0.994; 95% CI, 0.983-1.000), 17OHD (AUC, 0.993; 95% CI, 0.985-1.000), and 21OHD (AUC, 0.979; 95% CI, 0.964-0.994). For nonclassic 21OHD patients, the tool presented with significantly higher sensitivity compared with measurement of basal 17α-hydroxyprogesterone (17OHP) (0.973 vs 0.840, P = 0.005) and was not inferior to measurement of basal vs stimulated 17OHP (0.973 vs 0.947, P = 0.681). Conclusions The steroidogenesis score was biochemically interpretable and showed high accuracy in identifying CAH patients, especially for nonclassic 21OHD patients, thus offering a standardized approach to diagnose and subtype CAH.
Abstract Establishing a controllable information network security access management mechanism is the key task of power supply enterprise management, and it is also a key link to ensure enterprise information network security. In this article, we use a technology to intelligently obtain information about access devices. This technology is based on active and passive information collection. At the same time, it uses device portrait technology to intelligently identify network topology, device type and device status. And use an intelligent access mechanism to improve the controllability of information network security access.
Evidences indicate that inflammatory process plays pivotal role in tumor disease. Soluble epoxide hydrolase inhibitors (sEHIs) have been shown to participate in anti-inflammation and tumorigenesis by protecting epoxyeicosatrienoic acids (EETs). Although we have previously revealed some effects of t-AUCB on glioma in vitro, further investigations are needed to demonstrate its effects on glioblastoma growth in vivo and how to strengthen its antitumor effect. CCK-8 kit was used to test cell growth. Cell migration capacity was performed by wound healing assays. Transwell assay was used to test cell invasion potency. Cell-cycle analysis and cell apoptosis was performed by flow cytometry. The activity of caspase-3 in cells was measured using caspase-3 activity assay kits. Total RNA was extracted from cells lysated by TRIzol reagent. qRT-PCR was performed by ABI 7500 fast RT- PCR system. Lipofectamine RNAiMAX Transfection Reagent (Invitrogen) was used for siRNA transfection. Western blootting was used to test protein expression. Tumor cell xenograft mouse models were used for in vivo study. The SPSS version 17.0 software was applied for statistical analysis. Our data shown that t-AUCB inhibits cell proliferation, migration and invasion and induces cell cycle G1 phase arrest in vitro but induces no cell apoptosis; increased Hsp27 activation and following COX-2 overexpression confer resistance to t-AUCB treatment in glioblastoma both in vitro and in vivo; quercetin sensitizes glioblastoma to t-AUCB by dual inhibition of Hsp27 and COX-2 in vitro and in vivo. These results indicate that combination of t-AUCB and quercetin may be a potential approach to treating glioblastoma.
This paper examines the impact of uniform standards from an economy's perspective in the presence of capital crunches and economic shocks. We show that converting to uniform standards benefits some economies but may be detrimental to other economies, and the impact is determined by the joint effects of the difference in information quality, as well as capital endowments across economies. Our analysis indicates that economies with high information quality benefit from uniform standards when the capital crunch is severe, but may suffer if the capital crunch is relatively mild. We also show that a wealthy economy with a large capital endowment may be put at a disadvantage by converting to uniform standards. In addition, we find that improving information quality in one economy may have a positive or negative externality on other economies under uniform standards. Our analysis provides potential regulatory implications for standards setters and empirical implications for future research, and may help to inform the debates about uniform standards.
Abstract Background Demanding intensive care unit (ICU) work environments may lead to sleep disturbances in nurses, impacting their health and potentially patient safety. Yet, the prevalence remains unclear around the world. Aims To quantify the prevalence of sleep disturbances in intensive care nurses. Study Design Systematic review and meta‐analysis. A database search was conducted in Embase, PubMed, Web of Science, Scopus and CINAHL from their inception to April 2024 for relevant studies. Data from observational studies (cross‐sectional or cohort) that reported the prevalence of sleep disturbances, assessed using the Pittsburgh Sleep Quality Index (PSQI > 5), pooled in random‐effects meta‐analyses. Subgroup analyses were used to investigate variations in the prevalence estimates in terms of available variables. A Preferred Reporting Items for Systematic Reviews and Meta‐analyses (PRISMA)‐compliant protocol was registered in PROSPERO (CRD42023476428). Results In total, 24 articles were included in this study published from 1996 to 2023. Included studies were from 15 unique countries. Almost all of the studies were descriptive cross‐sectional studies ( n = 22; 91.7%). The included studies encompassed a range of intensive care nurses, from 42 to 605, involving a total of 3499 intensive care nurses. The reported proportion of intensive care nurses with sleep disturbances ranged from 20.0% to 100.0%, with a median of 76.7% (interquartile range: 62.9–85.7). The pooled prevalence of sleep disturbances in intensive care nurses was 75.1% (95% confidence interval: 37.2–53.1; 95% prediction interval: 30.5–95.4). Conclusions Sleep disturbance is a common issue in intensive care nurses. The study results highlight the importance of implementing effective interventions as early as possible to improve ICU sleep quality. Relevance to Clinical Practice High prevalence of sleep disturbances among intensive care nurses necessitates global interventions. Gender‐neutral approaches that acknowledge comparable risks and stable prevalence over time require long‐term strategies. Raising awareness through programmes is vital for implementing evidence‐based interventions to promote sleep health in intensive care nurses.
The promoter region of telomerase reverse transcriptase (TERTp) and isocitrate dehydrogenase (IDH) have been regarded as biomarkers with distinct clinical and phenotypic features. Investigated the possible correlations between tumor location and genetic alterations would enhance our understanding of gliomagenesis and heterogeneity of glioma. We examined mutations of TERTp and IDH by direct sequencing and fluorescence in-situ hybridization in a cohort of 225 grades II and III diffuse gliomas. Correlation analysis between molecular markers and tumor locations was performed by Chi-square tests/Fisher's exact test and multivariate logistic regression analysis. We found gliomas in frontal lobe showed higher frequency of TERTp mutation (P=0.0337) and simultaneously mutations of IDH and TERTp (IDH (mut)-TERTp(mut)) (P=0.0281) than frequency of biomarkers mutation of tumors in no-Frontal lobes, while lower frequency of TERTp mutation (P<0.0001) and simultaneously wild type of IDH and TERTp (IDH (wt)-TERTp(wt)) (P<0.0001) in midline than no-midline lobes. Logistic regression analysis indicated that locations of tumors associated with TERTp mutation (OR=0.540, 95% CI 0.324-0.900, P=0.018) and status of combinations of IDH and TERTp (IDH (mut)-TERTp (mut) vs. IDH (wt)-TERTp (wt) OR=0.162, 95% CI 0.075-0.350, P<0.001). In conclusion, grades II and III gliomas harboring TERTp mutation were located preferentially in the frontal lobe and rarely in midline. Association of IDH-TERTp status and tumor location suggests their potential values in molecular classification of grades II and III gliomas.
jabbrv-ltwa-all.ldf jabbrv-ltwa-en.ldf Long-term use of the immunosuppressant tacrolimus (Tac) is limited due to its nephrotoxic, hepatotoxic and diabetogenic effects. Up to 33.6% of solid organ transplantation patients receiving Tac treatment develop hyperglycemia; however, the underlying mechanisms remain poorly elucidated. Here, using a mouse model of Tac-induced hyperglycemia, we found that Tac-induced body-weight loss, hyperglycemia, hypoinsulinemia, glucose intolerance and insulin resistance were improved by a renin-angiotensin system (RAS) inhibitor (valsartan). Morphologic and immunofluorescence observation uncovered that the pancreatic islet areas and β cell mass were reduced in Tac-treated mice. Besides, in isolated islets from Tac-treated mice, markers of cell proliferation (Ki67, Ccna2 and Ccnd1) were downregulated but markers of cell apoptosis (DNA fragmentation, Bax and Caspase3) were upregulated compared with control mice. Hypoxia-related markers in pancreas, including hypoxia-inducible factor-1 (HIF-1) and its downstream factors (Adm, Hmox1 and Vegfa), CD31 and pimonidazole adducts were augmented by Tac. Treatment with Tac leaded to vascular dysfunction in pancreatic arteries. All of these adverse effects could be partly or fully restored by valsartan. Tac also increased levels of renin in renal tissue (1.00±0.06 vs 1.31±0.02, p<0.05) and serum (28.35±4.29 ng/mL vs 51.99±4.95 ng/mL, p<0.05). Inhibition of RAS by valsartan protected against vascular dysfunction induced by Tac in renal interlobar arteries. Collectively, our data illustrate a previously undescribed mechanism that Tac-induced vascular dysfunction in renal interlobar arteries leads to RAS activation. Blocking RAS by valsartan alleviated vascular dysfunction in dorsal pancreatic arteries and hypoxia in islets, which in turn prevents Tac-induced β-cell dysfunction and glucose metabolism disorder.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)