Cotepihl5278

Background Cardiovascular diseases contribute to the leading cause of deaths (31%) in the world population. Objective The objective of this study is to compile non-coding RNA-gene interaction into a core regulatory network whose dysregulation might play an important role in disease progression. Method We applied a structured approach to reconstruct the interaction network of lncRNAs, miRNAs and genes involved in cardiovascular diseases. For network construction, we used 'diseasome to interactome' and 'interactome to diseasome' approaches and developed two regulatory networks in heart disorders. In diseasome to interactome approach, starting from a disease-centric network we, expanded the data into an interaction network. However in interactome to diseasome, we used a set of guide genes, miRNAs and lncRNAs to arrive at the common diseases. The disease-centric network in combination with the interaction network will shed light on the interconnected components in a huge diseasome network implicated in heart disorders and manifested through small sub-networks while progressing. Using the above networks we created a sub-networks consisting only of hub genes, miRNAs and lncRNAs on both approaches. The dysregulation of any one of the hubs can lead to a disease condition. Results The top ranking hubs common in both the sub-networks were found to be VEGFA, MALAT1, HOTAIR, H19 and hsa-miR-15a. Our network based study reveals an entanglement of regulatory sub-network of miRNAs, lncRNAs and genes in multiple conditions. Conclusion The identification of hubs in the core triple node network of elements in disease development and progression demonstrates a promising role for network based approaches in targeting critical molecules for drug development.There is a broad spectrum of congenital anomalies of the central pulmonary arteries including abnormalities of development, origin, course and caliber. These anomalies incorporate simple lesions such as isolated pulmonary valve stenosis to very complex anomalies with many associated abnormalities. Part 1 and Part 2 of this review describe the range of anatomical variations that are encountered as well as important aspects of anatomy, physiology and surgical correction. The authors summarize and illustrate well-recognized as well as more complex anomalies to provide a broad and comprehensive understanding of these lesions and their appearances on CT and MR imaging. Part 1 covers anomalous development or origin of the main pulmonary artery.Diagnostic imaging of pediatric gastric masses often provides a challenge for the practicing radiologist. Radiologists should be aware of this relatively unusual pathology, particularly in cross-sectional imaging findings. We will review pediatric gastric masses and mass-like lesions, focusing on neoplastic and inflammatory etiologies.Background Burnout in medicine, and specifically radiology, has been receiving more attention. Little data-driven literature is available regarding risk factors/causes to ultimately help guide the development of potential solutions. Objective To survey pediatric radiologists, a cohort with a documented high prevalence of burnout, and to understand the impact of clinical demands on nonclinical tasks and the implications of burnout on mental health. Materials and methods A survey of Society for Pediatric Radiology (SPR) North America attendings was performed regarding institutional factors contributing to burnout, including call burden, clinical demands, departmental support and administrative/academic tasks. Questions regarding mental health and wellness resources were also included. Generalized linear modeling assuming binomial distribution was used for analyses with SAS 9.4. Results The response rate was 305/1,282 (24%) with 53% of respondents female. Respondents reported that both the number and complexity of clinical cases have increased since they first started practice as an attending, while the time for interpretation has not changed, P less then 0.0001. Using a scale of 0 (never), 1 (rarely), 2 (sometimes), 3 (frequently) and 4 (always), covering multiple hospitals (2.2) and administrative tasks (2.4) were the most stressful job factors. For those in administrative roles, the most stressful job factors were job-related tasks affected teaching duties (2.0) and decreased overall job satisfaction (2.0). Of the respondents, 52% said they know a physician affected by work stress-related mental illness and 25% know a physician who has contemplated or committed suicide. While 39% of the respondents have resources available to address burnout, only 33% utilize these resources. Conclusion Increasing clinical demands and additional institutional/departmental factors play a potential role in burnout, which has serious implications for the mental health of pediatric radiologists.Cell lines are powerful tools for research into liver function at the molecular level. However, they are generally unsuitable for rigorously assessing the effects of amino acid composition, because many lines require serum-containing medium for their maintenance. Here, we aimed to investigate the effects of ornithine and arginine, which are included in the characteristic metabolic process in hepatocyte, on a human hepatoma-derived cell line (FLC-4) that can be cultured in serum-free medium. FLC-4 cells were cultured under the following three conditions + ornithine/ - arginine, - ornithine/ - arginine, and -ornithine/ + arginine. Albumin expression evaluated by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay and showed no obvious differences based on the presence of ornithine or arginine. However, the mRNA levels of two liver-enriched transcription factors (CEBPB and HNF1A), which are involved in regulating albumin expression, were significantly higher in cells grown in medium-containing arginine than that in cells grown in ornithine-containing medium. Western blotting showed that the levels both activating and inhibitory C/EBPβ isoforms were significantly increased in cells grown in arginine medium. Furthermore, we have found that depletion of both ornithine and arginine, the polyamine sources, in the medium did not cause polyamine deficiency. When ornithine and arginine were depleted, albumin production was significantly reduced at the mRNA level, CEBPB mRNA levels were increased, and the level of activating form of C/EBPβ was increased. The results of this study suggest that in hepatocyte, these two amino acids might have different functions, and because of which they elicit disparate cellular responses.Malignant cells can increase in number using immune escape mechanisms such as immune checkpoints. In this study, we evaluated the expression of an immune checkpoint programmed death 1 (PD-1) on T-cell subsets in chronic myeloid leukemia (CML). We obtained bone marrow aspirate samples from CML patients and from individuals without evidence of hematologic malignancies (controls). PD-1 expression on T-cell subsets was measured using flow cytometric analysis. PD-1 expression levels on CD8+ T-cells were significantly lower in complete hematologic response (CHR) than in controls, chronic phase, and blast phase (BP). In CML patients receiving imatinib and dasatinib, PD-1 expression levels on CD8+ T-cells were lower than that at diagnosis. selleck products PD-1 expression levels on CD8+ T-cells were positively correlated with quantitative levels of the BCR/ABL fusion gene. PD-1 expression levels on CD4+ T-cells were higher in BP than in CHR. PD-1 expression levels on CD4+ T-cells did not differ significantly according to different medications or quantitative BCR/ABL1 fusion gene levels. Low PD-1 expression on CD8+ T-cells might play a role in maintaining CHR in CML patients. Immune monitoring of PD-1 expression on CD8+ T-cells may predict the disease course. In cases of refractory disease or resistance to imatinib or dasatinib, the use of PD-1 inhibitors would be helpful.Background Single-agent pembrolizumab represents the standard first-line option for metastatic non-small-cell lung cancer (NSCLC) patients with a PD-L1 (programmed death-ligand 1) expression of ≥ 50%. Methods We conducted a multicenter retrospective study aimed at evaluating the clinicopathologic correlates of pembrolizumab effectiveness in patients with treatment-naïve NSCLC and a PD-L1 expression of ≥ 50%. Results One thousand and twenty-six consecutive patients were included. The objective response rate (ORR) was 44.5% (95% CI 40.2-49.1), while the median progression free survival (PFS) and overall survival (OS) were 7.9 months (95% CI 6.9-9.5; 599 events) and 17.2 months (95% CI 15.3-22.3; 598 censored patients), respectively. ECOG-PS ≥ 2 (p less then 0.0001) and bone metastases (p = 0.0003) were confirmed to be independent predictors of a worse ORR. Former smokers (p = 0.0002), but not current smokers (p = 0.0532) were confirmed to have a significantly prolonged PFS compared to never smokers at multivaeness in clinical subgroups, such as patients with poorer PS and with liver/bone metastases, still remain to be addressed. We confirmed that the absence of tobacco exposure, and the presence of bone and liver metastasis are associated with worse clinical outcomes to pembrolizumab. Increasing levels of PD-L1 expression may help identifying a subset of patients who derive a greater benefit from pembrolizumab monotherapy.Purpose Patients with Graves' orbitopathy can present with asymmetric disease. The aim of this study was to identify clinical characteristics that distinguish asymmetric from unilateral and symmetric Graves' orbitopathy. Methods This was a multi-centre study of new referrals to 13 European Group on Graves' Orbitopathy (EUGOGO) tertiary centres. New patients presenting over a 4 month period with a diagnosis of Graves' orbitopathy were included. Patient demographics were collected and a clinical examination was performed based on a previously published protocol. Patients were categorized as having asymmetric, symmetric, and unilateral Graves' orbitopathy. The distribution of clinical characteristics among the three groups was documented. Results The asymmetric group (n = 83), was older than the symmetric (n = 157) group [mean age 50.9 years (SD 13.9) vs 45.8 (SD 13.5), p = 0.019], had a lower female to male ratio than the symmetric and unilateral (n = 29) groups (1.6 vs 5.0 vs 8.7, p less then 0.001), had more active disease than the symmetric and unilateral groups [mean linical Activity Score 3.0 (SD 1.6) vs 1.7 (SD 1.7), p less then 0.001 vs 1.3 (SD 1.4), p less then 0.001] and significantly more severe disease than the symmetric and unilateral groups, as measured by the Total Eye Score [mean 8.8 (SD 6.6) vs 5.3 (SD 4.4), p less then 0.001, vs 2.7 (SD 2.1), p less then 0.001]. Conclusion Older age, lower female to male ratio, more severe, and more active disease cluster around asymmetric Graves' orbitopathy. Asymmetry appears to be a marker of more severe and more active disease than other presentations. This simple clinical parameter present at first presentation to tertiary centres may be valuable to clinicians who manage such patients.Purpose Gene polymorphisms of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) and interleukin-6 (IL-6) may influence the risk of Graves' disease, but the results of so far published studies remain inconclusive. Therefore, the authors conducted this meta-analysis to assess relationships between TNF-α/IL-1/IL-6 polymorphisms and the risk of Graves' disease by pooling the findings of all relevant studies. Methods A comprehensive literature searching of Pubmed, Embase, Web of Science and CNKI was conducted by the authors, and twenty-eight studies were found to be eligible for pooled analyses. Results The pooled meta-analyses results showed that genotypic frequencies of TNF-α rs1800629, IL-1A rs1800587, IL-6 rs1800795 and IL-6 rs1800796 polymorphisms among patients with Graves' disease and control subjects differed significantly. Moreover, we found that genotypic frequencies of TNF-α rs1800629 and IL-6 rs1800795 polymorphisms among patients with Graves' disease and control subjects in Caucasians differed significantly, and genotypic frequencies of IL-1A rs1800587, IL-1B rs16944, IL-6 rs1800795 and IL-6 rs1800796 polymorphisms among patients with Graves' disease and control subjects in Asians also differed significantly.