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65. The 4-stage and 5-stage models achieved 68.5% (κ=0.54), and 64.1% (κ=0.51) accuracies, respectively. With the 5-stage model, the total sleep time was underestimated with mean (standard deviation) error of 7.5 (55.2) min. Conclusion The PPG-based deep learning model enabled accurate estimation of sleep time and differentiation between sleep stages with a moderate agreement to manual EEG-based scoring. As PPG is already included in ambulatory polygraphic recordings, applying the PPG-based sleep staging could improve their diagnostic value by enabling simple, low-cost, and reliable monitoring of sleep and help assess otherwise overlooked conditions such as REM-related OSA.Objectives Our goal was to assess the value of the Modified Arch Landing Areas Nomenclature (MALAN) for thoracic endovascular aortic repair (TEVAR), in which each landing area (LA) is identified by a proximal landing zone and the type of arch (e.g. 0/I), as predictors of postoperative proximal endograft performance. Methods A multicentre retrospective analysis was performed of patients treated with arch TEVAR (i.e. proximal landing zone 0-3) for various indications between 2007 and 2017. Patients were stratified by the MALAN classification into hostile LAs (i.e. 2/III and 3/III) and favourable LAs (i.e. 0/I-III, 1/I-III, 2/I-II and 3/I-II). Outcome criteria included composite proximal endograft failure (including type Ia endoleak, persistent false lumen perfusion at the level of the most proximal communication between the lumina in aortic dissections, endograft migration and retrograde dissection) and deaths from all causes. Competing risk analyses were performed. Results A total of 359 patients (hostile LAs 133; favourable LAs 226) were identified. The median age was 71.0 (62.0-77.0); 78.3% were men. Proximal endograft failure occurred in 28/133 patients (21.1%) in the hostile LA group and in 12/226 (5.3%) in the favourable LA group. On multivariate analysis, hostile LAs were independently associated with proximal endograft failure (P less then 0.0001). There was no other independent risk factor. Favourable LAs were associated with an increased mortality rate (P = 0.006), which could be attributed to the proximal LA subgroup (i.e. 0/I-III and 1/I-III) (P less then 0.0001), in addition to age (P less then 0.0001). Conclusions The MALAN classification identifies hostile proximal landing zones for TEVAR, namely 2/III and 3/III LAs, which are associated with dismal proximal endograft performance. The MALAN appears to be an intuitive and valuable tool to improve the preoperative decision-making process.Context Armadillo repeat containing 5 (ARMC5) on chromosome 16 is an adrenal gland tumor suppressor gene associated with primary aldosteronism, especially among African Americans (AAs). We examined the association of ARMC5 variants with aldosterone, plasma renin activity (PRA), blood pressure, glucose, and glycosylated hemoglobin A1c (HbA1c) in community-dwelling AAs. Methods The Jackson Heart Study is a prospective cardiovascular cohort study in AAs with baseline data collection from 2000 to 2004. Kernel machine method was used to perform a single joint test to analyze for an overall association between the phenotypes of interest (aldosterone, PRA, systolic and diastolic blood pressure [SBP, DBP], glucose, and HbA1c) and the ARMC5 single nucleotide variants (SNVs) adjusted for age, sex, BMI, and medications; followed by Baysian Lasso methodology to identify sets of SNVs in terms of associated haplotypes with specific phenotypes. Results Among 3223 participants (62% female; mean age 55.6 (SD ± 12.8) years), the average SBP and DBP were 127 and 76 mmHg, respectively. The average fasting plasma glucose and HbA1c were 101 mg/dL and 6.0%, respectively. ARMC5 variants were associated with all 6 phenotypes. Haplotype TCGCC (ch1631476015-31476093) was negatively associated, whereas haplotype CCCCTTGCG (ch1631477195-31477460) was positively associated with SBP, DBP, and glucose. Haplotypes GGACG (ch1631477790-31478013) and ACGCG (ch1631477834-31478113) were negatively associated with aldosterone and positively associated with HbA1c and glucose, respectively. Haplotype GCGCGAGC (ch1631471193-ch1631473597(rs114871627) was positively associated with PRA and negatively associated with HbA1c. Conclusions ARMC5 variants are associated with aldosterone, PRA, blood pressure, fasting glucose, and HbA1c in community-dwelling AAs, suggesting that germline mutations in ARMC5 may underlie cardiometabolic disease in AAs.Osteoblast cells are responsible for synthesizing new bone tissue, and determining how to control osteoblastic differentiation is vital to the treatment of osteoporosis. In the present study, we show that pentraxin 3 (PTX3) signaling is involved in the regulation of osteoblastic differentiation in MC3T3-E1 cells. Our data reveal that PTX3 is abundantly expressed in MC3T3-E1 cells and that its expression is inducible by the introduction of osteogenic induction medium (OIM). Overexpression of PTX3 was observed to significantly increase the expression of four osteoblast signature genes, including Runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), osteocalcin (OCN) and osterix (OSX), suggesting that the overexpression of PTX3 promotes osteoblastic differentiation. The relative level of gene expression between OIM and OIM plus overexpressed PTX3 was evaluated using the Affymetrix Gene Chip® mouse gene microarray. PTX3-related differentially expressed genes (DEGs) were screened. click here Gene ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes database (KEGG) pathway enrichment analyses were performed, and the PI3K/Akt signaling pathway was primarily involved in the osteogenic differentiation of PTX3. Protein-protein interactions (PPIs) were also constructed, and the molecular complex detection (MCODE) plugin calculated modules of PPI networks. Moreover, we show that the effect of PTX3 is mediated by its induction of the PI3K/Akt signaling pathway. Mechanistically, we show that the action of PTX3 requires the activation of PI3K and Akt, and deactivation of PI3K by its inhibitor LY294002 weakens the PTX3-mediated induction of osteoblast signature genes, ALP and matrix mineralization. The present study revealed a new role played by PTX3 and suggest a potential mechanism governing the osteoblastic differentiation of MC3T3-E1 cells.Lipid synthesis is the recently found metabolism of cancer cells after their metastasis to lymph nodes (LNs). Carbonic acid is the main byproduct of the lipid metabolism in such cells which resulted in acidification of LN ambient. Hence, calibrated pH sensing could be a diagnostic method to find involved LNs. Here, we designed a simple pH sensing method by a syringe containing sterile PBS and embedded by litmus paper to intraoperatively check the pH of LN fluid. Injected phosphate buffer saline (PBS) would homogenize the LN fluid and litmus needle would detect the pH of the LN. We presented an experimental pathological calibration for the pH values in correlation with cancerous states of the LNs. This system named metabolism based metastatic lymph diagnoser (MMLD) could be a real-time noninvasive tool for precise and fast diagnosis of involved LNs.X-ray crystallography is the major approach for determining atomic-level protein structures. Because not all proteins can be easily crystallized, accurate prediction of protein crystallization propensity provides critical help in guiding experimental design and improving the success rate of X-ray crystallography experiments. This study has developed a new machine-learning-based pipeline that uses a newly developed deep-cascade forest (DCF) model with multiple types of sequence-based features to predict protein crystallization propensity. Based on the developed pipeline, two new protein crystallization propensity predictors, denoted as DCFCrystal and MDCFCrystal, have been implemented. DCFCrystal is a multistage predictor that can estimate the success propensities of the three individual steps (production of protein material, purification and production of crystals) in the protein crystallization process. MDCFCrystal is a single-stage predictor that aims to estimate the probability that a protein will pass thr solvent accessibility of residues. Meanwhile, the new crystal-dataset constructions help to train the models with more comprehensive crystallization knowledge.The present study was designed to investigate the role of amylin, H2S, and connexin 43 in vascular dysfunction and enhanced ischemia-reperfusion (I/R)-induced myocardial injury in diabetic rats. A single dose of streptozotocin (65 mg/kg) was employed to induce diabetes mellitus. After 8 weeks, there was a significant decrease in the plasma levels of amylin, an increase in I/R injury to isolated hearts (increase in CK-MB and cardiac troponin release) on the Langendorff apparatus. Moreover, there was a significant impairment in vascular endothelium function as assessed by quantifying acetylcholine-induced relaxation in norepinephrine-precontracted mesenteric arteries. There was also a marked decrease in the expression of H2S and connexin 43 in the hearts following I/R injury in diabetic rats. Treatment with amylin agonist, pramlintide (100 and 200 µg/kg), and H2S donor, NaHS (10 and 20 μmol/kg) for 2 weeks improved the vascular endothelium function, abolished enhanced myocardial injury and restored the levels of H2S along with connexin 43 in diabetic animals. However, pramlintide and NaHS failed to produce these effects the presence of gap junction blocker, carbenoxolone (20 and 40 mg/kg). Carbenoxolone also abolished the myocardial levels of connexin 43 without affecting the plasma levels of amylin and myocardial levels of H2S. The decrease in the amylin levels with a consequent reduction in H2S and connexin 43 may contribute to inducing vascular dysfunction and enhancing I/R-induced myocardial injury in diabetic rats.Background Evidence remains inconsistent regarding the potential influence of β-blocker (BB) use on clinical outcomes in women with breast cancer. We aimed to evaluate the association between BB and prognosis of breast cancer in an updated meta-analysis. Methods Follow-up studies comparing the clinical outcomes of breast cancer in women with and without use of BB were included by search of PubMed, Embase, and Cochrane's Library. A random-effect model was used to pool the results. Results Seventeen observational studies were included. Pooled results did not support a significant association between BB use and breast cancer recurrence (risk ratio [RR] = 0.85, 95% confidence interval [CI] 0.68-1.07, P=0.17), breast cancer related deaths (RR = 0.83, 95% CI 0.65-1.06, P=0.14), or all-cause deaths (RR = 1.01, 95% CI 0.91-1.11, P=0.91) in women with breast cancer. Study characteristics such as sample size, definition of BB use, follow-up durations, adjustment of menopausal status, or quality score did not significantly affect the results. Subgroup analyses showed that BB may be associated with a trend of reduced risk of all-cause deaths in women with breast cancer in prospective studies (two datasets, RR = 0.81, P=0.05), but not in retrospective studies (eight datasets, RR = 1.06, P=0.16; P for subgroup analyses = 0.02). Conclusions Current evidence from observational studies does not support a significant association between BB use and improved prognosis in women with breast cancer.
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