No enhancement and a smooth non-enhancing margin on MRI were predictive of longer PFS, while a smooth non-enhancing margin was a significant predictor of longer OS in LGGs. Textural analyses of MR imaging data predicted IDH1 mutation, 1p/19q codeletion, histological grade, and tumor progression with high accuracy.

Accurate identification of axillary lymph node (ALN) involvement in patients with early-stage breast cancer is important for determining appropriate axillary treatment options and therefore avoiding unnecessary axillary surgery and complications. Here, we report deep learning radiomics (DLR) of conventional ultrasound and shear wave elastography of breast cancer for predicting ALN status preoperatively in patients with early-stage breast cancer. Clinical parameter combined DLR yields the best diagnostic performance in predicting ALN status between disease-free axilla and any axillary metastasis with areas under the receiver operating characteristic curve (AUC) of 0.902 (95% confidence interval [CI]: 0.843, 0.961) in the test cohort. This clinical parameter combined DLR can also discriminate between low and heavy metastatic burden of axillary disease with AUC of 0.905 (95% CI: 0.814, 0.996) in the test cohort. Our study offers a noninvasive imaging biomarker to predict the metastatic extent of ALN for patients with early-stage breast cancer.

Two groups of tau, 3R-and 4R-tau, are generated by alternative splicing of tau exon 10. Normal adult human brain expresses equal levels of them. Disruption of the physiological balance is a common feature of several tauopathies. Very early in their life, individuals with Down syndrome (DS) develop Alzheimer-type tau pathology, the molecular basis for which is not fully understood. Here, we demonstrate that Dyrk1A, a kinase encoded by a gene in the DS critical region, phosphorylates alternative splicing factor (ASF) at Ser-227, Ser-234, and Ser-238, driving it into nuclear speckles and preventing it from facilitating tau exon 10 inclusion. The increased dosage of Dyrk1A in DS brain due to trisomy of chromosome 21 correlates to an increase in 3R-tau level, which on abnormal hyperphosphorylation and aggregation of tau results in neurofibrillary degeneration. Imbalance of 3R-and 4R-tau in DS brain by Dyrk1A-induced dysregulation of alternative splicing factor-mediated alternative splicing of tau exon 10 represents a novel mechanism of neurofibrillary degeneration and may help explain early onset tauopathy in individuals with DS.The microtubule-associated protein tau plays an important role in the polymerization and stabilization of neuronal microtubules. Tau is thus crucial to both the maintenance of the neuronal cytoskeleton and the maintenance of the axonal transport. Abnormal hyperphosphorylation and accumulation of this protein into neurofibrillary tangles (NFTs) 2 in neurons, first discovered in Alzheimer disease (AD) brain (1, 2), is now known to be a characteristic of several related neurodegenerative disorders called tauopathies (3). Several different etiopathogenic mechanisms lead to development of NFTs (4). Adult human brain expresses six isoforms of tau from a single gene by alternative splicing of its pre-mRNA (5, 6). Inclusion or exclusion of exon 10 (E10), which codes for the second microtubule-binding repeat, divides tau isoforms into two main groups, three (3R)-or four (4R)-microtubule-binding repeat tau. They show key differences in their interactions with tau kinases as well as their biological function in the polymerization and stabilization of neuronal microtubules. In the adult human brain, 3R-tau and 4R-tau are expressed at similar levels (5, 7). Several specific mutations in the tau gene associated with frontotemporal dementias with Parkinsonism linked to chromosome 17 (FTDP-17) cause dysregulation of tau E10 splicing, leading to a selective increase in either 3R-tau or 4R-tau. It has therefore been suggested that equal levels of 3R-tau and 4R-tau may be critical for maintaining optimal neuronal physiology (8).Down syndrome (DS), caused by partial or complete trisomy of chromosome 21, is the most common chromosomal disorder and one of the leading causes of mental retardation in humans. Individuals with DS develop Alzheimer-type neurofibrillary degeneration as early as the fourth decade of life (9). The presence of Alzheimer-type amyloid pathology in DS is attributed to an extra copy of APP gen...

Proximal spinal muscular atrophy (SMA) is a common motor neuron disorder caused by mutation of the telomeric survival of motor neuron gene SMN1. The centromeric survival of motor neuron SMN2 gene is retained in all SMA patients but does not produce sufficient SMN protein to prevent the development of clinical symptoms. The SMN1 and SMN2 genes differ functionally by a single nucleotide change. This change affects the efficiency with which exon 7 is incorporated into the mRNA transcript. Thus, SMN2 produces less full-length mRNA and protein than SMN1. We have screened a library of compounds in order to identify ones that can alter the splicing pattern of the SMN2 gene. Here, we report that the compound aclarubicin increases the retention of exon 7 into the SMN2 transcript. We show that aclarubicin effectively induces incorporation of exon 7 into SMN2 transcripts from the endogenous gene in type I SMA fibroblasts as well as into transcripts from a SMN2 minigene in the motor neuron cell line NSC34. In type I fibroblasts, treatment resulted in an increase in SMN protein and gems to normal levels. Our results suggest that alteration of splicing pattern represents a new approach to modification of gene expression in disease treatment and demonstrate the feasibility of high throughput screens to detect compounds that affect the splicing pattern of a gene.

Background Peripheral subpleural solitary pulmonary nodules can be visualized and resected easily at thoracoscopy, but it is very difficult to localize deep nonpalpable pulmonary nodules that lie in lung parenchyma. The purpose of this article was to study the effectiveness of video-assisted thoracoscopic solitary pulmonary nodules resection after computed tomography (CT)-guided hookwire localization and to review the literature related to solitary pulmonary nodule diagnosis and treatment. Methods From April 2008 to June 2009, 43 patients with a solitary pulmonary nodule who had undergone CT-guided hookwire localization and video-assisted thoracoscopic surgery (VATS) were studied. Results Two cases were considered unsuccessful, other patients underwent CT-guided hookwire localization successfully, and ten patients had an asymptomatic minimal pneumothorax that did not require any intervention. The diameter of nodules ranged from 5 to 30 mm as measured by CT (mean 17.2 ± 7.5 mm). The distance between the center of nodule and visceral pleural ranged from 2 to 40 mm (mean 18.5 ± 9.3 mm). Of the 41 scheduled VATS procedures, 38 patients underwent thoracoscopic wedge resection. Twenty-two of 41 patients who revealed primary lung cancer after frozen-section examination underwent VATS lobectomy and lymphadenectomy. Three patients were converted to thoracotomy, and a major postoperative hemothorax occurred in one patient. No intra-or postoperative mortality or morbidity was recorded. Conclusions Video-assisted thoracoscopic solitary pulmonary nodule resection after CT-guided hookwire localization is a safe and effective procedure for accurate diagnosis and resection of indeterminate solitary pulmonary nodules.

The survival motor neuron (SMN) protein forms cytoplasmic granules when overexpressed. We report here that SMN co-localizes with TIA-1/R and G3BP, protein assemblers of stress granules (SGs), and that SMN is co-immunoprecipitated with TIA-1/R, suggesting that SMN granules are SGs. Formation of SMN granules precedes accumulation of TIA-1/R, indicating that SMN serves as a facilitator of SG formation. However, the exon 7 skipping product, SMND7, is largely retained in the nucleus and forms nuclear granules, indicating that exon 7 is critical for SG formation. Our findings reveal a novel SMN function and possible SG involvement in the pathogenesis of spinal muscular atrophy.

Interferons (IFNs) can serve as the first line of immune defense against viral infection. The identification of IFN-λs 1, 2, 3 & 4 (termed as type III IFNs) has revealed that the antiviral immune response to viruses contains more components than the type I IFNs that have been known for more than 50 years. IFN-λs are IFN-λ1 (IL-29), IFN-λ2 (IL-28a), IFN-λ3 (IL-28b) and IFN-λ4, which resembles IFN-λ3. IFN-λs have type I-IFN-like immune responses and biological activities, but our knowledge of these novel players in the antiviral response is not well established. In this review, we try to describe the current information on the expression and function of IFN-λs in the innate antiviral immune defense and IFN-λ2’s role in regulating and shaping the adaptive immune response. We suggest that IFN-λs are key antiviral cytokines, directly performing an antiviral immune response at epithelial surfaces in the early stages of viral infection, and that these cytokines also skew the balance of Th1 and Th2 cells to Th1 phenotype. In addition, genetic polymorphisms in IFN-λ genes can impair antiviral immune responses in clinical treatment.

Background: Use of contrast material-enhanced (CE) US Liver Imaging Reporting and Data System (LI-RADS) version 2017 has not been validated in large populations where hepatitis B virus (HBV) is endemic. Purpose: To evaluate the diagnostic performance of CE US LI-RADS version 2017 in a population with a high prevalence of HBV infection. Materials and Methods: In this retrospective study, liver nodules in patients with HBV who were evaluated from January 2004 to December 2016 were categorized as CE US LR-1 to LR-5 through LR-M. A subgroup of LR-M nodules was reclassified as LR-5, and additional analysis was performed. The reference standard consisted of histologic evaluation or composite imaging and clinical follow-up findings. Diagnostic performance was assessed with sensitivity, specificity, positive predictive value (PPV), and negative predictive value. Results: A total of 2020 nodules in 1826 patients (median age, 54 years 6 12 [standard deviation]; 1642 men) were included. Of the 1159 LR-5 lesions, 1141 were hepatocellular carcinoma (HCC); three, intrahepatic cholangiocarcinomas; six, other malignancies; six, atypical hyperplasia; and three, benign lesions. The PPV of LR-5 for HCC was 98% (95% confidence interval [CI]: 98%, 99%). In LR-M nodules, 153 showed arterial phase hyperenhancement, early washout, and absence of punched-out appearance within 5 minutes, and 142 of 153 (93%; 95% CI: 89%, 97%) were HCC. If these nodules were reclassified as LR-5, LR-M specificity and PPV as a predictor of non-HCC malignancy increased from 88% (95% CI: 87%, 89%) and 36% (95% CI: 31%, 41%) to 96% (95% CI: 95%, 97%) and 58% (95% CI: 51%, 65%), respectively (P , .001). Despite reclassification, LR-5 specificity and PPV remained high (94% [95% CI: 92%, 96%] and 98% [95% CI: 97%, 99%], respectively). Conclusion: The contrast-enhanced US Liver Imaging Reporting and Data System version 2017 category LR-5 is effectively predictive of the presence of hepatocellular carcinoma. In patients with hepatitis B virus infection, performance may be further improved by reclassification of category LR-M nodules with arterial phase hyperenhancement, early washout, and no punched-out appearance to LR-5. Published under a CC BY 4.0 license.