Identification of a region within the placental alkaline phosphatase mRNA that mediates p180-dependent targeting to the endoplasmic reticulum.

In both eukaryotic and prokaryotic cells, it has been recently established that mRNAs encoding secreted and membrane proteins can be localized to the surface of membranes via both translation-dependent and RNA element-mediated mechanisms. Previously, we showed that the placental alkaline phosphatase (ALPP) mRNA can be localized to the ER membrane independently of translation, and this localization is mediated by p180, an mRNA receptor present in the ER. In this article, we aimed to identify the cis-acting RNA element in ALPP. Using chimera constructs containing fragments of the ALPP mRNA, we demonstrate that the ER-localizing RNA element is present within the 3' end of the open reading frame and codes for a transmembrane domain. In addition, we show that this region requires p180 for efficient ER anchoring. Taken together, we provide the first insight into the nature of cis-acting ER-localizing RNA elements responsible for localizing mRNAs on the ER in mammalian cells.

An integrative non-invasive malignant brain tumors classification and Ki-67 labeling index prediction pipeline with radiomics approach.

BACKGROUND: The histological sub-classes of brain tumors and the Ki-67 labeling index (LI) of tumor cells are major factors in the diagnosis, prognosis, and treatment management of patients. Many existing studies primarily focused on the classification of two classes of brain tumors and the Ki-67LI of gliomas. This study aimed to develop a preoperative non-invasive radiomics pipeline based on multiparametric-MRI to classify-three types of brain tumors, glioblastoma (GBM), metastasis (MET) and primary central nervous system lymphoma (PCNSL), and to predict their corresponding Ki-67LI. METHODS: In this retrospective study, 153 patients with malignant brain tumors were involved. The radiomics features were extracted from three types of MRI (T1-weighted imaging (T1WI), fluid-attenuated inversion recovery (FLAIR), and contrast-enhanced T1-weighted imaging (CE-T1WI)) with three masks (tumor core, edema, and whole tumor masks) and selected by a combination of Pearson correlation coefficient (CORR), LASSO, and Max-Relevance and Min-Redundancy (mRMR) filters. The performance of six classifiers was compared and the top three performing classifiers were used to construct the ensemble learning model (ELM). The proposed ELM was evaluated in the training dataset (108 patients) by 5-fold cross-validation and in the test dataset (45 patients) by hold-out. The accuracy (ACC), sensitivity (SEN), specificity (SPE), F1-Score, and the area under the receiver operating characteristic curve (AUC) indicators evaluated the performance of the models. RESULTS: The best feature sets and ELM with the optimal performance were selected to construct the tri-categorized brain tumor aided diagnosis model (training dataset AUC: 0.96 (95% CI: 0.93, 0.99); test dataset AUC: 0.93) and Ki-67LI prediction model (training dataset AUC: 0.96 (95% CI: 0.94, 0.98); test dataset AUC: 0.91). The CE-T1WI was the best single modality for all classifiers. Meanwhile, the whole tumor was the most vital mask for the tumor classification and the tumor core was the most vital mask for the Ki-67LI prediction. CONCLUSION: The developed radiomics models led to the precise preoperative classification of GBM, MET, and PCNSL and the prediction of Ki-67LI, which could be utilized in clinical practice for the treatment planning for brain tumors.

A Novel Subtraction Method to Reduce Metal Artifacts of Cerebral Aneurysm Embolism Coils.

OBJECTIVE: To investigate a novel subtraction method (S-MAR), combing metal artifact reduction (MAR), virtual monochromatic imaging (VMI), and subtraction CT angiography (CTA) to remove the metal artifacts of coils after endovascular embolotherapy of intracranial aneurysms. METHOD: In this retrospective study, 29 patients with 38 coils after endovascular embolotherapy of intracranial aneurysms who underwent cerebral CTA using a dual-layer detector spectral CT were included. Conventional CT images (CI), virtual non-enhanced (VNC) images and VMI ranging from 40 to 120 KeV in steps of 10 were reconstructed. These images were then postprocessed to CIMAR, VMIMAR and VNCMAR with MAR software (O-MAR; Philips Healthcare, Cleveland, OH, USA). The novel subtraction method (S-MAR) was derived from subtraction imaging between VNCMAR and the optimal VMIMAR. Contrast-to-noise (CNR) and Noise(Background) of CI, CIMAR, VMI, and VMIMAR were calculated quantitatively. Two Independent radiologists qualitatively assessed artifacts in all images using coil artifact score (CA score), a 5-point Likert scale. Besides, all coils were divided into two groups (group 1: diameter < 5.0 mm, group 2: diameter ≥ 5.0 mm). Differences between two groups were statistically analyzed. RESULTS: The optimal KeV was 40 KeV. Strong correlations between diameter of coils and the CA score of CI were found (rs = 0.652, P < 0.05). CNR, Noise and CA score were significantly improved by CIMAR and VMIMAR compared with CI (P < 0.05). The S­MAR showed significantly better performance compared with CI, CIMAR, VMI, and VMIMAR in reducing metal coil artifacts according to the CA score (P < 0.05), especially in group 2. CONCLUSION: The novel S­MAR proved to be a promising method to reduce coil metal artifacts and elevate the vessel visualization adjacent to coils. It could develop to be widely used in cerebral CTA after coiled aneurysms.

Numb exon 9 inclusion regulates Integrinß5 surface expression and promotes breast cancer metastasis.

The endocytic adaptor protein Numb acts as a tumor suppressor through downregulation of oncogenic pathways in multiple cancer types. The identification of splicing alterations giving rise to changes in Numb protein isoform expression indicate that Numb also has tumor promoting activity, though the underlying mechanisms are unknown. Here we report that NUMB exon 9 inclusion, which results in production of a protein isoform with an additional 49 amino acids, is a feature of multiple cancer types including all subtypes of breast cancer and correlates with worse progression-free survival. Specific deletion of exon 9-included Numb isoforms (Exon9in) from breast cancer cells reduced cell growth and prevents spontaneous lung metastasis in a mouse model. Quantitative proteome profiling showed that loss of Exon9in causes downregulation of membrane receptors and adhesion molecules, as well as proteins involved in extracellular matrix organization and the epithelial-mesenchymal transition (EMT) state. In addition, exon 9 deletion caused remodeling of the endocytic network, decreased ITGß5 surface localization, cell spreading on vitronectin and downstream signaling to ERK and SRC. Together these observations suggest that Exon9in isoform expression disrupts the endocytic trafficking functions of Numb, resulting in increased surface expression of ITGß5 as well as other plasma membrane proteins to promote cell adhesion, EMT, and tumor metastasis.

Simple Technique for Transscleral Fixation of a Foldable Posterior Chamber Intraocular Lens Using a Single Suture.

Objective: To explore the simplified technique for transscleral fixation of a foldable posterior chamber intraocular lens (IOLs) in patients with aphakia or inadequate posterior capsule support. Methods: A review was conducted of 18 eyes of eighteen patients with the absence of-or inadequate-capsule support, after the simplified technique of using a foldable posterior chamber intraocular lens (PC IOLs) with stable four-point transscleral fixation, as performed by a skilled surgeon. This technique uses only a single suture and a knot to fix a PC IOL firmly without creating a scleral flap. The mean follow-up time was 18 ± 5.8 months (ranging from 12 to 24 months). Results: All patients exhibited improved visual acuity. No IOL tilt or dislocation or iris capture was observed, and all patients exhibited stable and centered IOL after surgery. No complex complications, such as suture shedding and exposure, corneal endothelial decompensation, persistent uveitis, or retinal detachment and endophthalmitis were observed. Conclusion: The simplified technique proposed here is a reliable, economical, and reproducible method of treating patients with aphakia or inadequate posterior capsule support. It provides excellent IOL stability, reduces surgical duration and complexity, and prevents certain complications.

Partial splenic embolization has beneficial effects for the management of gastroesophageal variceal hemorrhage.

BACKGROUND/AIMS: Partial splenic embolization (PSE) is used in the management of gastroesophageal variceal hemorrhage (GEVH). However, it is uncertain whether it has beneficial effects for GEVH patients in preventing variceal recurrence and variceal hemorrhage, as well as promoting overall survival (OS), when it is combined with conventional therapies. MATERIALS AND METHODS: The databases including PubMed, EMBASE, Web of Science, Google scholar, and Cochrane Central Register of Controlled Trials were searched up to 11th of November, 2015. Meta-analyses were performed by using Review Manager 5.3 software for analyzing the risk of bias, Newcastle-Ottawa Scale for assessing the bias of cohort studies, and GRADEprofiler software for assessing outcomes obtained from the meta-analyses. RESULTS: A total of 1505 articles were reviewed, and 1 randomized controlled trial and 5 cohort studies with 244 participants were eligible for inclusion. The pooled hazard ratio (HR) of variceal recurrence is 0.50 (95% confidence interval (CI) 0.37, 0.68; P< 0.00001; I2 = 0%). The pooled HR of variceal hemorrhage is 0.24 (95% CI 0.15, 0.39; P< 0.00001; I2 = 0%). The pooled HR of OS is 0.50 (95% CI 0.33, 0.67; P< 0.00001; I2 = 0%). Meta-analyses demonstrated statistically significant superiority of combinational therapies over conventional therapies in preventing variceal recurrence and variceal hemorrhage and prolonging OS. The complications related to PSE were mild or moderate and nonfatal. CONCLUSIONS: The results indicate that PSE has beneficial effects for GEVH patients, however, future investigation with a larger number of subjects in clinical trials is warranted.