1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018.

ObjectiveTo identify the differences among preinvasive lesions, minimally invasive adenocarcinomas (MIAs) and invasive pulmonary adenocarcinomas (IPAs) based on radiomic feature analysis with computed tomography (CT).MethodsA total of 109 patients with ground-glass opacity lesions (GGOs) in the lungs determined by CT examinations were enrolled, all of whom had received a pathologic diagnosis. After the manual delineation and segmentation of the GGOs as regions of interest (ROIs), the patients were subdivided into three groups based on pathologic analyses: the preinvasive lesions (including atypical adenomatous hyperplasia and adenocarcinoma in situ) subgroup, the MIA subgroup and the IPA subgroup. Next, we obtained the texture features of the GGOs. The data analysis was aimed at finding both the differences between each pair of the groups and predictors to distinguish any two pathologic subtypes using logistic regression. Finally, a receiver operating characteristic (ROC) curve was applied to accurately evaluate the performances of the regression models. ResultsWe found that the voxel count feature (P<0.001) could be used as a predictor for distinguishing IPAs from preinvasive lesions. However, the surface area feature (P=0.040) and the extruded surface area feature (P=0.013) could be predictors of IPAs compared with MIAs. In addition, the correlation feature (P=0.046) could distinguish preinvasive lesions from MIAs better.ConclusionsPreinvasive lesions, MIAs and IPAs can be discriminated based on texture features within CT images, although the three diseases could all appear as GGOs on CT images. The diagnoses of these three diseases are very important for clinical surgery.

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Unveiling the principles governing embryonic stem cell (ESC) differentiation into specific lineages is critical for understanding embryonic development and for stem cell applications in regenerative medicine. Here, we establish an intersection between LIF-Stat3 signaling that is essential for maintaining murine (m) ESCs pluripotency, and the glycolytic enzyme, the platelet isoform of phosphofructokinase (Pfkp). In the pluripotent state, Stat3 transcriptionally suppresses Pfkp in mESCs while manipulating the cells to lift this repression results in differentiation towards the ectodermal lineage. Pfkp exhibits substrate specificity changes to act as a protein kinase, catalyzing serine phosphorylation of the developmental regulator Lin41. Such phosphorylation stabilizes Lin41 by impeding its autoubiquitination and proteasomal degradation, permitting Lin41-mediated binding and destabilization of mRNAs encoding ectodermal specification markers to favor the expression of endodermal specification genes. This provides new insights into the wiring of pluripotency-differentiation circuitry where Pfkp plays a role in germ layer specification during mESC differentiation.

Exploiting the pluripotent properties of embryonic stem cells (ESCs) holds great promise for regenerative medicine. Nevertheless, directing ESC differentiation into specialized cell lineages requires intricate control governed by both intrinsic and extrinsic factors along with the actions of specific signaling networks. Here, we reveal the involvement of the p21-activated kinase 4 (Pak4), a serine/threonine kinase, in sustaining murine ESC (mESC) pluripotency. Pak4 is highly expressed in R1 ESC cells compared with embryonic fibroblast cells and its expression is progressively decreased during differentiation. Manipulations using knockdown and overexpression demonstrated a positive relationship between Pak4 expression and the clonogenic potential of mESCs. Moreover, ectopic Pak4 expression increases reprogramming efficiency of Oct4-Klf4-Sox2-Myc-induced pluripotent stem cells (iPSCs) whereas Pak4-knockdown iPSCs were largely incapable of generating teratomas containing mesodermal, ectodermal and endodermal tissues, indicative of a failure in differentiation. We further establish that Pak4 expression in mESCs is transcriptionally driven by the core pluripotency factor Nanog which recognizes specific binding motifs in the Pak4 proximal promoter region. In turn, the increased levels of Pak4 in mESCs fundamentally act as an upstream activator of the Akt pathway. Pak4 directly binds to and phosphorylates Akt at Ser473 with the resulting Akt activation shown to attenuate downstream GSK3β signaling. Thus, our findings indicate that the Nanog-Pak4-Akt signaling axis is essential for maintaining mESC self-renewal potential with further importance shown during somatic cell reprogramming where Pak4 appears indispensable for multi-lineage specification.

Background Existing classification neglected integrity of the clitoral hood-labia minora complex (CLC) and various anatomic variations, resulting in the failure to optimize a tailored approach to individuals. Objectives In this study, we presented a new classification system for comprehensive evaluation of the CLC variations and introduced a simple surgical approach for the fused type. Methods We classified the anatomic variations of the CLC as three types. Type 1 was the isolated labia minora or lateral clitoral hood hypertrophy. Type 2 was the conventional combined hypertrophy. Type 3 was the fused lateral clitoral hood and labia minora. The modified procedure for the fused type was performed in four steps: the anterior border of labia minora was defined first, then the hypertrophic lateral clitoral hood and labia minora were removed separately, and finally the junction region was trimmed. Satisfaction questionnaires were conducted during follow-ups. Results Among all 301 patients (602 sides), type 2 was the most common variation (285 sides, 47.3%). Type 3 variations in 67 patients (105 sides, 17.5%) were identified, and 77.6% of the patients answered the questionnaires 3 months after surgery. The satisfaction rate in the four-step excision group was 91.7%, which was significantly higher than that in the wedge excision group (56.3%) (P =0.01). The complication rate of the four-step excision was 2.5%. Conclusions Preoperative evaluation based on the new classification facilitated recognition of the variations of CLC, especially of the fused type. The four-step excision is a simple, effective and safe approach to treat the fused variation with high satisfaction.

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