- Upregulation of miR‑132‑3p in cholangiocarcinoma tissues: A study based on RT‑qPCR, The Cancer Genome Atlas miRNA sequencing, Gene Expression Omnibus microarray data and bioinformatics analyses. [Journal Article]Mol Med Rep 2019MM
- MicroRNAs (miRNAs/miRs) have been reported to be closely associated with numerous human diseases, including cholangiocarcinoma (CCA). However, the number of miRNAs known to be involved in CCA is limited, and the association between miR‑132‑3p and CCA remains unknown. In the present study, the clinical role of miR‑132‑3p and its potential signaling pathways were investigated by multiple approaches…
MicroRNAs (miRNAs/miRs) have been reported to be closely associated with numerous human diseases, including cholangiocarcinoma (CCA). However, the number of miRNAs known to be involved in CCA is limited, and the association between miR‑132‑3p and CCA remains unknown. In the present study, the clinical role of miR‑132‑3p and its potential signaling pathways were investigated by multiple approaches. Reverse transcription‑quantitative PCR (RT‑qPCR), CCA‑associated Gene Expression Omnibus (GEO), ArrayExpress and Sequence Read Archive (SRA) miRNA‑microarray or miRNA‑sequencing data were screened, and meta‑analyses were conducted, in order to calculate the receiver operating characteristic (ROC) curve and standardized mean difference (SMD). The predicted target genes of miR‑132‑3p were obtained from 12 online databases and were combined with the downregulated differentially expressed genes identified in the RNA‑sequencing data of CCA. Gene Ontology annotation and pathway analysis were performed in WebGestalt. Protein‑protein interaction analyses were conducted in STRING. The Cancer Genome Atlas (TCGA) mRNA expression profiles were used to validate the expression levels of hub genes at the mRNA level. The Human Protein Atlas was used to identify the protein expression levels of hub genes in CCA tissues and non‑tumor biliary epithelium. The meta‑analyses comprised 10 groups of RT‑qPCR data, eight GEO microarray datasets and one TCGA miRNA‑sequencing dataset. The SMD of miR‑132‑3p in CCA was 0.75 (95% CI: 0.25, 1.24), which indicated that miR‑132‑3p was overexpressed in CCA tissues. This finding was supported by a summary ROC value of 0.80 (95% CI: 0.76, 0.83). The pooled sensitivity and specificity were 0.81 (95% CI: 0.59, 0.93) and 0.71 (95% CI: 0.58, 0.81), respectively. The relative expression level of miR‑132‑3p in the early stage of CCA (stages I‑II) was 6.8754±0.5279, which was markedly lower than that in the advanced stage (stages III‑IVB), 7.3034±0.3267 (P=0.003). Consistently, the miR‑132‑3p level in low‑grade CCA (grades G1‑G2) was 6.7581±0.5297, whereas it was 7.1191±0.4651 in patients with high‑grade CCA (grades G3‑G4) (P=0.037). Furthermore, 555 potential target genes of miR‑132‑3p in CCA were mainly enriched in the 'Focal Adhesion‑PI3K‑Akt‑mTOR‑signaling pathway'. In conclusion, upregulation of miR‑132‑3p may serve a pivotal role in the tumorigenesis and progression of CCA by targeting different pathways. Further in vitro and in vivo studies are required to support the current findings.
- Google search activity in early psychosis: A qualitative analysis of internet search query content in first episode psychosis. [Journal Article]Early Interv Psychiatry 2019EI
- CONCLUSIONS: Individuals with early psychosis appear to be using the Internet for obtaining information about their early symptoms and experiences prior to their first contact with psychiatric care. Improving our understanding of the ways by which individuals with emerging psychosis search for information about their experiences online may help mental health clinicians tailor online resources in hopes of improving pathways to care and reducing the duration of untreated psychosis.
- Long noncoding RNA TPT1-AS1 downregulates the microRNA-770-5p expression to inhibit glioma cell autophagy and promote proliferation through STMN1 upregulation. [Journal Article]J Cell Physiol 2019JC
- Through the microarray analysis, long noncoding RNA TPT1-AS1 (TPT1-AS1) was identified in the development of glioma. However, the specific effect of TPT1-AS1 on glioma autophagy in the recent years has not fully been investigated. Therefore, the purpose of our present study is to investigate the function of TPT1-AS1 on affecting autophagy of glioma cells through regulation of microRNA-770-5p (miR…
Through the microarray analysis, long noncoding RNA TPT1-AS1 (TPT1-AS1) was identified in the development of glioma. However, the specific effect of TPT1-AS1 on glioma autophagy in the recent years has not fully been investigated. Therefore, the purpose of our present study is to investigate the function of TPT1-AS1 on affecting autophagy of glioma cells through regulation of microRNA-770-5p (miR-770-5p)-mediated stathmin 1 (STMN1). Initially, the expression of TPT1-AS1, miR-770-5p, and STMN1 were determined in glioma cell lines, followed by the prediction and validation of their interaction. After that, the effects of TPT1-AS1, miR-770-5p, and STMN1 on the in vitro glioma cell proliferation and autophagy were assessed using EdU assay and macrophage-derived chemokine (MDC) and on the in vivo tumor development and autophagy were evaluated using a nude mouse xenograft tumor assay and immunofluorescence assay. In comparison with the normal cells, the glioma cells displayed upregulated expression of TPT1-AS1 and STMN1, but a downregulated miR-770-5p expression. miR-770-5p, which directly targeted STMN1, could be downregulated by TPT1-AS1. Subsequently, in glioma cells, TPT1-AS1 can function to competitively bind to miR-770-5p, thus regulatEing STMN1 expression. Moreover, glioma cell proliferation and autophagy could be mediated through the TPT1-AS1/miR-770-5p/STMN1 axis. From our data we conclude an inhibitory function of TPT1-AS1 in glioma cell autophagy by downregulating miR-770-5p and upregulating STMN1, which may be instrumental for the therapeutic targeting and clinical management of glioma.
- A Novel Fully Automated Mri-Based Deep Learning Method for Classification of Idh Mutation Status in Brain Gliomas. [Journal Article]Neuro Oncol 2019NO
- CONCLUSIONS: We demonstrate high IDH classification accuracy using only T2-weighted MR images. This represents an important milestone towards clinical translation.
- Systematic Online Academic Resource (SOAR) Review: Renal and Genitourinary. [Review]AEM Educ Train 2019; 3(4):375-386AE
- CONCLUSIONS: We demonstrated the feasibility of systematically identifying and curating FOAM resources for a specific EM topic and identified an overrepresentation of some subtopics. This curated list of resources may guide trainees, teacher recommendations, and resource producers. Further entries in the series will address other topics relevant to EM.
- The Jewish Pathologist Carl Julius Rothberger (1871-1945) and the gradual deprivation of his rights in the Third Reich. [Journal Article]Pathol Res Pract 2019; :152679PR
- The Jewish pathologist Carl Julius Rothberger (1871-1945) is undoubtedly one of the most important representatives of his field. His studies on atrial fibrillation, the bundle branch block and arrhythmia perpetua in particular secured him a place in medical history. Rothberger also gave the name to an agar used to prove the neutral red reduction of salmonella (Rothberger-Scheffler agar). While Ro…
The Jewish pathologist Carl Julius Rothberger (1871-1945) is undoubtedly one of the most important representatives of his field. His studies on atrial fibrillation, the bundle branch block and arrhythmia perpetua in particular secured him a place in medical history. Rothberger also gave the name to an agar used to prove the neutral red reduction of salmonella (Rothberger-Scheffler agar). While Rothberger's name is well known in pathology, his biography and his experiences of stigmatization as a Jewish university lecturer have received little attention. The latter are therefore the focus of this paper. Three central research questions need to be answered: What effect did Rothberger's Jewish origins have on his personal life and on his career at the University of Vienna in the first third of the 20th century? What personal changes resulted from the "Anschluss" ("annexation") of Austria to the German Reich (1938) and the assumption of power by the National Socialists? And finally, what role does Rothberger play in the collective memory of the city of Vienna today - does a kind of public memory exist? The current work is based on extensive primary sources from the Archives of the University of Vienna, the manuscript collection of the Archives of the Medical Faculty there and the Austrian State Archives. Some of these primary sources have been evaluated for the first time. They have been supplemented by contemporary newspaper articles and the relevant secondary literature. Although Rothberger grew up in a largely assimilated upper middle-class family in which religious practice hardly played a role, he was exposed to considerable anti-Semitic and repressive actions, especially from the 1920s onwards. However, these repressions only become apparent at second glance. Stages of increasing rights deprivation included (1) Rothberger's frustratingly unsuccessful applications for the Chair of General and Experimental Pathology, which had been vacant since 1924, (2) his forced early retirement (1936/37), (3) an exclusion order against him along with temporary imprisonment after the "annexation" (1938), and (4) the final closure of the institute which he had helped develop and shape over decades (1942). An active public debate on the victims of National Socialism has been taking place in Vienna and at its university since the turn of the millennium. In this context, Carl Julius Rothberger was officially commemorated at a ceremony in 2010 - a late attempt to rescue him and his work from collective oblivion.
- An Association between Right Ventricular Dysfunction and Sudden Cardiac Death. [Journal Article]Heart Rhythm 2019HR
- CONCLUSIONS: RV dysfunction was associated with a significantly increased risk of SCD independent of LVEF, and when combined with LVEF, had additive effects on SCD risk.
- Morbidity in Patients With Separation of Cartilaginous Framework: Temporoparietal Fascia Flap and Treatment With Dermal Regeneration Template. [Journal Article]J Craniofac Surg 2019JC
- CONCLUSIONS: Coverage with dermal regeneration template and random occipito-temporal fascia flap as an alternative use instead of temporoparietal fascial flaps, offers good postoperative results, lower operating times, and similar rate of complications, with the advantage of producing no visible scars and reserve the temporoparietal fascial flap for possible exposure of the cartilaginous framework.
- Assessment of 19 Genes and Validation of CRM Gene Panel for Quantitative Transcriptional Analysis of Molecular Rejection and Inflammation in Archival Kidney Transplant Biopsies. [Journal Article]Front Med (Lausanne) 2019; 6:213FM
- Background: There is an urgent need to develop and implement low cost, high-throughput standardized methods for routine molecular assessment of transplant biopsies. Given the vast archive of formalin-fixed and paraffin-embedded (FFPE) tissue blocks in transplant centers, a reliable protocol for utilizing this tissue bank for clinical validation of target molecules as predictors of graft outcome …
Background: There is an urgent need to develop and implement low cost, high-throughput standardized methods for routine molecular assessment of transplant biopsies. Given the vast archive of formalin-fixed and paraffin-embedded (FFPE) tissue blocks in transplant centers, a reliable protocol for utilizing this tissue bank for clinical validation of target molecules as predictors of graft outcome over time, would be of great value. Methods: We designed and optimized assays to quantify 19 target genes, including previously reported set of tissue common rejection module (tCRM) genes. We interrogated their performance for their clinical utility for detection of graft rejection and inflammation by analyzing gene expression microarrays analysis of 163 renal allograft biopsies, and subsequently validated in 40 independent FFPE archived kidney transplant biopsies at a single center. Results: A QPCR (Fluidigm) and a barcoded oligo-based (NanoString) gene expression platform were compared for evaluation of amplification of gene expression signal for 19 genes from degraded RNA extracted from FFPE biopsy sections by a set protocol. Increased expression of the selected 19 genes, that reflect a combination of specific cellular infiltrates (8/19 genes) and a graft inflammation score (11/19 genes which computes the tCRM score allowed for segregation of kidney transplant biopsies with stable allograft function and normal histology from those with histologically confirmed acute rejection (AR; p = 0.0022, QPCR; p = 0.0036, barcoded assay) and many cases of histological borderline inflammation (BL). Serial biopsy shaves used for gene expression were also processed for in-situ hybridization (ISH) for a subset of genes. ISH confirmed a high degree of correlation of signal amplification and tissue localization. Conclusions: Target gene expression amplification across a custom set of genes can identify AR independent of histology, and quantify inflammation from archival kidney transplant biopsy tissue, providing a new tool for clinical correlation and outcome analysis of kidney allografts, without the need for prospective kidney biopsy biobanking efforts.
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- A probabilistic classifier ensemble weighting scheme based on cross-validated accuracy estimates. [Journal Article]Data Min Knowl Discov 2019; 33(6):1674-1709DM
- Our hypothesis is that building ensembles of small sets of strong classifiers constructed with different learning algorithms is, on average, the best approach to classification for real-world problems. We propose a simple mechanism for building small heterogeneous ensembles based on exponentially weighting the probability estimates of the base classifiers with an estimate of the accuracy formed t…
Our hypothesis is that building ensembles of small sets of strong classifiers constructed with different learning algorithms is, on average, the best approach to classification for real-world problems. We propose a simple mechanism for building small heterogeneous ensembles based on exponentially weighting the probability estimates of the base classifiers with an estimate of the accuracy formed through cross-validation on the train data. We demonstrate through extensive experimentation that, given the same small set of base classifiers, this method has measurable benefits over commonly used alternative weighting, selection or meta-classifier approaches to heterogeneous ensembles. We also show how an ensemble of five well-known, fast classifiers can produce an ensemble that is not significantly worse than large homogeneous ensembles and tuned individual classifiers on datasets from the UCI archive. We provide evidence that the performance of the cross-validation accuracy weighted probabilistic ensemble (CAWPE) generalises to a completely separate set of datasets, the UCR time series classification archive, and we also demonstrate that our ensemble technique can significantly improve the state-of-the-art classifier for this problem domain. We investigate the performance in more detail, and find that the improvement is most marked in problems with smaller train sets. We perform a sensitivity analysis and an ablation study to demonstrate the robustness of the ensemble and the significant contribution of each design element of the classifier. We conclude that it is, on average, better to ensemble strong classifiers with a weighting scheme rather than perform extensive tuning and that CAWPE is a sensible starting point for combining classifiers.