GAFlow: Incorporating Gaussian Attention into Optical Flow

Optical flow, or the estimation of motion fields from image sequences, is one of the fundamental problems in computer vision. Unlike most pixel-wise tasks that aim at achieving consistent representations of the same category, optical flow raises extra demands for obtaining local discrimination and smoothness, which yet is not fully explored by existing approaches. In this paper, we push Gaussian Attention (GA) into the optical flow models to accentuate local properties during representation learning and enforce the motion affinity during matching. Specifically, we introduce a novel Gaussian-Constrained Layer (GCL) which can be easily plugged into existing Transformer blocks to highlight the local neighborhood that contains fine-grained structural information. Moreover, for reliable motion analysis, we provide a new Gaussian-Guided Attention Module (GGAM) which not only inherits properties from Gaussian distribution to instinctively revolve around the neighbor fields of each point but also is empowered to put the emphasis on contextually related regions during matching. Our fully-equipped model, namely Gaussian Attention Flow network (GAFlow), naturally incorporates a series of novel Gaussian-based modules into the conventional optical flow framework for reliable motion analysis. Extensive experiments on standard optical flow datasets consistently demonstrate the exceptional performance of the proposed approach in terms of both generalization ability evaluation and online benchmark testing. Code is available at https://github.com/LA30/GAFlow.Comment: To appear in ICCV-202

Using RNase sequence specificity to refine the identification of RNA-protein binding regions

Massively parallel pyrosequencing is a high-throughput technology that can sequence hundreds of thousands of DNA/RNA fragments in a single experiment. Combining it with immunoprecipitation-based biochemical assays, such as cross-linking immunoprecipitation (CLIP), provides a genome-wide method to detect the sites at which proteins bind DNA or RNA. In a CLIP-pyrosequencing experiment, the resolutions of the detected protein binding regions are partially determined by the length of the detected RNA fragments (CLIP amplicons) after trimming by RNase digestion. The lengths of these fragments usually range from 50-70 nucleotides. Many genomic regions are marked by multiple RNA fragments. In this paper, we report an empirical approach to refine the localization of protein binding regions by using the distribution pattern of the detected RNA fragments and the sequence specificity of RNase digestion. We present two regions to which multiple amplicons map as examples to demonstrate this approach

Identification of transcription factor and microRNA binding sites in responsible to fetal alcohol syndrome

This is a first report, using our MotifModeler informatics program, to simultaneously identify transcription factor (TF) and microRNA (miRNA) binding sites from gene expression microarray data. Based on the assumption that gene expression is controlled by combinatorial effects of transcription factors binding in the 5'-upstream regulatory region and miRNAs binding in the 3'-untranslated region (3'-UTR), we developed a model for (1) predicting the most influential cis-acting elements under a given biological condition, and (2) estimating the effects of those elements on gene expression levels. The regulatory regions, TF and miRNA, which mediate the differential genes expression in fetal alcohol syndrome were unknown; microarray data from alcohol exposure paradigm was used. The model predicted strong inhibitory effects of 5' cis-acting elements and stimulatory effects of 3'-UTR under alcohol treatment. Current predictive model derived a key hypothesis for the first time a novel role of miRNAs in gene expression changes associated with abnormal mouse embryo development after alcohol exposure. This suggests that disturbance of miRNA functions may contribute to the alcohol-induced developmental deficiencies

A Possible Reason to Induce Acute Graft-vs.-Host Disease After Hematopoietic Stem Cell Transplantation: Lack of Sirtuin-1 in CD4+ T Cells

Sirtuin 1 (SIRT1) is a critical suppressor of T cell immunity. However, whether SIRT1 is involved in the progression of acute graft-vs.-host disease (aGVHD) has still remained unclear. PI3K/Akt/mTOR pathway is a crucial element involved in the activation and functions of T cells. Over-activation of PI3K/Akt/mTOR signaling may be related to the occurrence of aGVHD. STAT3 activation requires phosphorylation and acetylation. A recent study showed that STAT3 hyperphosphorylation in CD4+ T cells may be a trigger of aGVHD. The role of the STAT3 acetylation in aGVHD pathogenesis is still unclear. The present study revealed that SIRT1 deficiency as a critical factor is involved in the excessive activation of mTOR pathway and upregulation of STAT3 acetylation and phosphorylation in CD4+ T cells from patients with aGVHD. Exorbitant activation of IL-1β signaling is the main reason for TAK1-dependent SIRT1 insufficiency. The findings of the present study might provide a new therapeutic target for treating aGVHD

Pharmacokinetics, tissue distribution, and metabolites of a polyvinylpyrrolidone-coated norcantharidin chitosan nanoparticle formulation in rats and mice, using LC-MS/MS

A novel formulation containing polyvinylpyrrolidone (PVP) K30-coated norcantharidin (NCTD) chitosan nanoparticles (PVP–NCTD–NPs) was prepared by ionic gelation between chitosan and sodium tripolyphosphate. The average particle size of the PVP–NCTD–NPs produced was 140.03 ± 6.23 nm; entrapment efficiency was 56.33% ± 1.41%; and drug-loading efficiency was 8.38% ± 0.56%. The surface morphology of NCTD nanoparticles (NPs) coated with PVP K30 was characterized using various analytical techniques, including X-ray diffraction and atomic force microscopy. NCTD and its metabolites were analyzed using a sensitive and specific liquid chromatography-tandem mass spectrometry method with samples from mice and rats. The results indicated the importance of the PVP coating in controlling the shape and improving the entrapment efficiency of the NPs. Pharmacokinetic profiles of the NCTD group and PVP–NCTD–NP group, after oral and intravenous administration in rats, revealed that relative bioavailabilities were 173.3% and 325.5%, respectively. The elimination half-life increased, and there was an obvious decrease in clearance. The tissue distribution of NCTD in mice after the intravenous administration of both formulations was investigated. The drug was not quantifiable at 6 hours in all tissues except for the liver and kidneys. The distribution of the drug in the liver and bile was notably improved in the PVP–NCTD–NP group. The metabolites and excretion properties of NCTD were investigated by analyzing rat feces and urine samples, collected after oral administration. A prototype drug and two metabolites were found in the feces, and seven metabolites in the urine. The primary elimination route of NCTD was via the urine. The quantity of the parent drug eliminated in the feces of the PVP–NCTD–NP group, was 32 times greater than that of the NCTD group, indicating that the NPs dramatically increased the reduction quantity from liver to bile. We conclude that PVP–NCTD–NPs are an adequate formulation for enhancing the absorption of NCTD, and significantly improving therapeutic effects targeting the hepatic system. Decarboxylation and hydroxylation were the dominant metabolic pathways for NCTD. Metabolites were mainly excreted into rat kidney and finally into urine

Four novel variants identified in primary hyperoxaluria and genotypic and phenotypic analysis in 21 Chinese patients

Background: Primary hyperoxaluria (PH) is a rare genetic disorder characterized by excessive accumulation of oxalate in plasma and urine, resulting in various phenotypes due to allelic and clinical heterogeneity. This study aimed to analyze the genotype of 21 Chinese patients with primary hyperoxaluria (PH) and explore their correlations between genotype and phenotype.Methods: Combined with clinical phenotypic and genetic analysis, we identified 21 PH patients from highly suspected Chinese patients. The clinical, biochemical, and genetic data of the 21 patients were subsequently reviewed.Results: We reported 21 cases of PH in China, including 12 cases of PH1, 3 cases of PH2 and 6 cases of PH3, and identified 2 novel variants (c.632T > G and c.823_824del) in AGXT gene and 2 novel variants (c.258_272del and c.866-34_866-8del) in GRHPR gene, respectively. A possible PH3 hotspot variant c.769T > G was identified for the first time. In addition, patients with PH1 showed higher levels of creatinine and lower eGFR than those with PH2 and PH3. In PH1, patients with severe variants in both alleles had significantly higher creatinine and lower eGFR than other patients. Delayed diagnosis still existed in some late-onset patients. Of all cases, 6 had reached to end-stage kidney disease (ESKD) at diagnosis with systemic oxalosis. Five patients were on dialysis and three had undergone kidney or liver transplants. Notably, four patients showed a favorable therapeutic response to vitamin B6, and c.823_824dup and c.145A > C may be identified as potentially vitamin B6-sensitive genotypes.Conclusion: In brief, our study identified 4 novel variants and extended the variant spectrum of PH in the Chinese population. The clinical phenotype was characterized by large heterogeneity, which may be determined by genotype and a variety of other factors. We first reported two variants that may be sensitive to vitamin B6 therapy in Chinese population, providing valuable references for clinical treatment. In addition, early screening and prognosis of PH should be given more attention. We propose to establish a large-scale registration system for rare genetic diseases in China and call for more attention on rare kidney genetic diseases

YAP/TAZ-CDC42 signaling regulates vascular tip cell migration

Angiogenesis and vascular remodeling are essential for the establishment of vascular networks during organogenesis. Here we show that the Hippo signaling pathway effectors YAP and TAZ are required, in a gene dosage-dependent manner, for the proliferation and migration of vascular endothelial cells (ECs) during retinal angiogenesis. Intriguingly, nuclear translocation of YAP and TAZ induced by Lats1/2-deletion blocked endothelial migration and phenocopied Yap/Taz-deficient mutants. Furthermore, overexpression of a cytoplasmic form of YAP (YAPS127D) partially rescued the migration defects caused by loss of YAP and TAZ function. Finally, we found that cytoplasmic YAP positively regulated the activity of the small GTPase CDC42, deletion of which caused severe defects in endothelial migration. These findings uncover a previously unrecognized role of cytoplasmic YAP/TAZ in promoting cell migration by activating CDC42 and provide insight into how Hippo signaling in ECs regulates angiogenesis

Comparisons between cross-section and long-axis-section in the quantification of aneurysmal wall enhancement of fusiform intracranial aneurysms in identifying aneurysmal symptoms

BackgroundTo investigate the quantification of aneurysmal wall enhancement (AWE) in fusiform intracranial aneurysms (FIAs) and to compare AWE parameters based on different sections of FIAs in identifying aneurysm symptoms.MethodsConsecutive patients were prospectively recruited from February 2017 to November 2019. Aneurysm-related symptoms were defined as sentinel headache and oculomotor nerve palsy. All patients underwent high resolution magnetic resonance imaging (HR-MRI) protocol, including both pre and post-contrast imaging. CRstalk (signal intensity of FIAs' wall divided by pituitary infundibulum) was evaluated both in the cross-section (CRstalk−cross) and the long-axis section (CRstalk−long) of FIAs. Aneurysm characteristics include the maximal diameter of the cross-section (Dmax), the maximal length of the long-axis section (Lmax), location, type, and mural thrombus. The performance of parameters for differentiating symptomatic and asymptomatic FIAs was obtained and compared by a receiver operating characteristic (ROC) curve.ResultsForty-three FIAs were found in 43 patients. Eighteen (41.9%) patients who presented with aneurysmal symptoms were classified in the symptomatic group. In univariate analysis, male sex (P = 0.133), age (P = 0.013), FIAs type (P = 0.167), mural thrombus (P = 0.130), Lmax (P = 0.066), CRstalk−cross (P = 0.027), and CRstalk−long (P = 0.055) tended to be associated with aneurysmal symptoms. In the cross-section model of multivariate analysis, male (P = 0.038), age (P = 0.018), and CRstalk−cross (P = 0.048) were independently associated with aneurysmal symptoms. In the long-axis section model of multivariate analysis, male (P = 0.040), age (P = 0.010), CRstalk−long (P = 0.046), and Lmax (P = 0.019) were independently associated with aneurysmal symptoms. In the combination model of multivariate analysis, male (P = 0.027), age (P = 0.011), CRstalk−cross (P = 0.030), and Lmax (P = 0.020) were independently associated with aneurysmal symptoms. CRstalk−cross has the highest accuracy in predicting aneurysmal symptoms (AUC = 0.701). The combination of CRstalk−cross and Lmax exhibited the highest performance in discriminating symptomatic from asymptomatic FIAs (AUC = 0.780).ConclusionAneurysmal wall enhancement is associated with symptomatic FIAs. CRstalk−cross and Lmax were independent risk factors for aneurysmal symptoms. The combination of these two factors may improve the predictive performance of aneurysmal symptoms and may also help to stratify the instability of FIAs in future studies

Multiple imaging modality-guided radiofrequency ablation combined with transarterial chemoembolization for hepatocellular carcinoma in special locations

PURPOSEWe aimed to evaluate the safety and effectiveness of radiofrequency ablation (RFA) combined with transarterial chemoembolization (TACE) guided by multiple imaging modalities for hepatocellular carcinomas (HCCs) in special (i.e., high-risk or unfavorable) locations compared with those in conventional locations.METHODSA total of 122 HCC patients were enrolled, including 85 patients (69.7%) with HCC in conventional locations and 37 (30.3%) with HCC in special locations. The clinical data, overall survival (OS), progression-free survival (PFS), and procedure-related adverse events were analyzed.RESULTSRFA combined with TACE was successfully performed in all patients. Three complications (2.5%) occurred, with no significant difference between the conventional (n=1, 1.2%) and special (n=2, 5.4%) locations (P = 0.218). Complete tumor necrosis rate was not significantly different between the conventional (n=73, 85.9%) and special (n=34, 91.9%) locations at one-month imaging (P = 0.353). After a follow-up of 3–48 months, the PFS was 17 months for patients with HCC in conventional locations and 14 months for patients with HCC in special locations; one-year PFS rate was 68.1% in the conventional location group, not significantly (P = 0.741) different from 59.1% in the special location group. The OS was 28 months in the conventional location group while 32 months in the special location group. The cumulative one- and two-year OS rates were 89.9% and 63.3%, respectively, in the conventional location group, not significantly different from 96.3% and 65% in the special location group (P = 0.273). Age (P = 0.043) and tumor size (P < 0.001) were significant prognostic factors for OS, and tumor size (P < 0.001) was the only significant prognostic factor for PFS.CONCLUSIONRFA guided by multiple imaging modalities combined with TACE may be safe and effective for treating HCCs in special locations