Quantitative peritumoral magnetic resonance imaging fingerprinting improves machine learning-based prediction of overall survival in colorectal cancer

Aim: To investigate magnetic resonance imaging (MRI)-based peritumoral texture features as prognostic indicators of survival in patients with colorectal liver metastasis (CRLM). Methods: From 2007–2015, forty-eight patients who underwent MRI within 3 months prior to initiating treatment for CRLM were identified. Clinicobiological prognostic variables were obtained from electronic medical records. Ninety-four metastatic hepatic lesions were identified on T1-weighted post-contrast images and volumetrically segmented. A total of 112 radiomic features (shape, first-order, texture) were derived from a 10 mm region surrounding each segmented tumor. A random forest model was applied, and performance was tested by receiver operating characteristic (ROC). Kaplan-Meier analysis was utilized to generate the survival curves. Results: Forty-eight patients (male:female = 23:25, age 55.3 years ± 18 years) were included in the study. The median lesion size was 25.73 mm (range 8.5–103.8 mm). Microsatellite instability was low in 40.4% (38/94) of tumors, with Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation detected in 68 out of 94 (72%) tumors. The mean survival was 35 months ± 21 months, and local disease progression was observed in 35.5% of patients. Univariate regression analysis identified 42 texture features [8 first order, 5 gray level dependence matrix (GLDM), 5 gray level run time length matrix (GLRLM), 5 gray level size zone matrix (GLSZM), 2 neighboring gray tone difference matrix (NGTDM), and 17 gray level co-occurrence matrix (GLCM)] independently associated with metastatic disease progression (P < 0.03). The random forest model achieved an area under the curve (AUC) of 0.88. Conclusions: MRI-based peritumoral heterogeneity features may serve as predictive biomarkers for metastatic disease progression and patient survival in CRLM

A Single Atrial Extrastimulus Can Distinguish Sinus Tachycardia from 1:1 Paroxysmal Tachycardia

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72755/1/j.1540-8159.1986.tb06671.x.pd

L'Est et l'Ouest face à la chute du Mur

La chute du Mur de Berlin le 9 novembre 1989 a surpris le monde entier. Il est tombé aussi rapidement qu'il avait été construit : en une nuit. Avec le recul, l'événement apparaît en réalité comme un épisode - certes très important par lui-même - dans un processus qui a commencé quelques mois, et même quelques années auparavant, et dont les prolongements se font ressentir jusqu'à aujourd'hui, dans un monde devenu pourtant très différent. Mais quelles furent les réactions, en Europe et ailleurs, dans la période qui a suivi ce choc ? Une fois passée la stupeur - quasi-générale, et au-delà des scènes de joie de nombreux citoyens du monde entier relayées par les médias, les attitudes face à cet événement ont été, d'Est en Ouest, fort diverses. Elles sont fonction de la situation politique et géopolitique du pays concerné et de ses intérêts à ce moment-là, de son rapport à l'Allemagne passée et présente, et elles dépendent bien sûr aussi des dirigeants alors en place. George Bush, François Mitterrand, Mikhaïl Gorbatchev, Nicolae Ceauşescu, Margaret Thatcher, Fidel Castro ou encore les dirigeants coréens, pour n'en citer que quelques-uns, ont nécessairement eu un regard très différent sur l'événement. Question de perspective donc, comme le montrent les contributions présentées dans cet ouvrage. Après une remise en contexte des enjeux de la construction du Mur puis de sa chute, sont analysés ici les craintes et les espoirs suscités par une situation totalement nouvelle, et qui semblait pouvoir devenir incontrôlable. La lisibilité d'un monde jusqu'alors clairement divisé en deux blocs disparaît soudainement, l'ordre issu de la seconde guerre mondiale est remis en cause, sans que les contours de la nouvelle donne ne soient encore perceptibles

Impact of schizophrenia GWAS loci converge onto distinct pathways in cortical interneurons vs glutamatergic neurons during development

Remarkable advances have been made in schizophrenia (SCZ) GWAS, but gleaning biological insight from these loci is challenging. Genetic influences on gene expression (e.g., eQTLs) are cell type-specific, but most studies that attempt to clarify GWAS loci\u27s influence on gene expression have employed tissues with mixed cell compositions that can obscure cell-specific effects. Furthermore, enriched SCZ heritability in the fetal brain underscores the need to study the impact of SCZ risk loci in specific developing neurons. MGE-derived cortical interneurons (cINs) are consistently affected in SCZ brains and show enriched SCZ heritability in human fetal brains. We identified SCZ GWAS risk genes that are dysregulated in iPSC-derived homogeneous populations of developing SCZ cINs. These SCZ GWAS loci differential expression (DE) genes converge on the PKC pathway. Their disruption results in PKC hyperactivity in developing cINs, leading to arborization deficits. We show that the fine-mapped GWAS locus in the ATP2A2 gene of the PKC pathway harbors enhancer marks by ATACseq and ChIPseq, and regulates ATP2A2 expression. We also generated developing glutamatergic neurons (GNs), another population with enriched SCZ heritability, and confirmed their functionality after transplantation into the mouse brain. Then, we identified SCZ GWAS risk genes that are dysregulated in developing SCZ GNs. GN-specific SCZ GWAS loci DE genes converge on the ion transporter pathway, distinct from those for cINs. Disruption of the pathway gene CACNA1D resulted in deficits of Ca2+ currents in developing GNs, suggesting compromised neuronal function by GWAS loci pathway deficits during development. This study allows us to identify cell type-specific and developmental stage-specific mechanisms of SCZ risk gene function, and may aid in identifying mechanism-based novel therapeutic targets

Analysis of Outcomes in Ischemic vs Nonischemic Cardiomyopathy in Patients With Atrial Fibrillation A Report From the GARFIELD-AF Registry

IMPORTANCE Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes