H-VFI: Hierarchical Frame Interpolation for Videos with Large Motions

Capitalizing on the rapid development of neural networks, recent video frame interpolation (VFI) methods have achieved notable improvements. However, they still fall short for real-world videos containing large motions. Complex deformation and/or occlusion caused by large motions make it an extremely difficult problem in video frame interpolation. In this paper, we propose a simple yet effective solution, H-VFI, to deal with large motions in video frame interpolation. H-VFI contributes a hierarchical video interpolation transformer (HVIT) to learn a deformable kernel in a coarse-to-fine strategy in multiple scales. The learnt deformable kernel is then utilized in convolving the input frames for predicting the interpolated frame. Starting from the smallest scale, H-VFI updates the deformable kernel by a residual in succession based on former predicted kernels, intermediate interpolated results and hierarchical features from transformer. Bias and masks to refine the final outputs are then predicted by a transformer block based on interpolated results. The advantage of such a progressive approximation is that the large motion frame interpolation problem can be decomposed into several relatively simpler sub-tasks, which enables a very accurate prediction in the final results. Another noteworthy contribution of our paper consists of a large-scale high-quality dataset, YouTube200K, which contains videos depicting a great variety of scenarios captured at high resolution and high frame rate. Extensive experiments on multiple frame interpolation benchmarks validate that H-VFI outperforms existing state-of-the-art methods especially for videos with large motions

Assessment of different classification systems for predicting the risk of superior laryngeal nerve injury during thyroid surgery: a prospective cohort study

BackgroundA multitude of anatomical variations have been noted in the external branch of the superior laryngeal nerve (EBSLN). In this study, intraoperative neuromonitoring (IONM) was used to assess the potential value of the different classical EBSLN classifications for predicting the risk of EBSLN injury.MethodsIn total, 136 patients with thyroid nodules were included in this prospective cohort study, covering 242 nerves at risk (NAR). The EBSLN was identified by observing the cricothyroid muscle twitch and/or typical electromyography (EMG) biphasic waveform. The EBSLNs were classified by Cernea classification, Kierner classification, and Friedman classification, respectively. The EMG parameters and outcomes of vocal acoustic assessment were recorded.ResultsThe distribution of Cernea, Kiernea, and Friedman subtypes were, respectively, Cernea 1 (40.9%), Cernea 2A (45.5%), Cernea 2B (10.7%), Kierner 1 (40.9%), Kierner 2 (45.5%), Kierner 3 (10.7%), Kierner 4 (2.9%) and Friedman 1 (15.7%), Friedman 2 (33.9%), Friedman 3 (50.4%). The amplitudes of EBSLN decreased significantly after superior thyroid pole operation, respectively, in Cernea 2A (193.7 vs. 226.6μV, P=0.019), Cernea 2B (185.8 vs. 221.3μV, P=0.039), Kierner 2 (193.7vs. 226.6μV, P=0.019), Kierner 3 (185.8 vs. 221.3μV, P=0.039), Kierner 4 (126.8vs. 226.0μV, P=0.015) and Friedman type 2 (184.8 vs. 221.6μV, P=0.030). There were significant differences in Fmax and Frange for Cernea 2A (P=0.001, P=0.001), 2B (P=0.001, P=0.038), Kierner 2 (P=0.001), Kierner 3 (P=0.001, P=0.038), and Friedman 2 (P=0.004, P=0.014). In the predictive efficacy of EBSLN injury, the Friedman classification showed higher accuracy (69.8% vs. 44.3% vs. 45.0%), sensitivity (19.5% vs. 11.0% vs. 14.0%), and specificity (95.6% vs. 89.9% vs. 89.9%) than the Cernea and Kierner classifications. However, the false negative rate of Friedman classification was significantly higher than other subtypes (19.5% vs. 11.0% vs. 14.0%).ConclusionCernea 2A and 2B; Kierner 2, 3, and 4; and Friedman 2 were defined as the high-risk subtypes of EBSLN. The risk prediction ability of the Friedman classification was found to be superior compared to other classifications

The relationship between subclinical hypothyroidism and invasive papillary thyroid cancer

BackgroundSubclinical hypothyroidism is the most common thyroid dysfunction. Approximately 10% of patients with thyroid cancer have subclinical hypothyroidism. There is a paucity of real-world studies examining the relationship between subclinical hypothyroidism and known correlates of invasiveness of papillary thyroid carcinoma (PTC).Materials and methodsA retrospective cohort study of 13,717 patients with PTC was conducted. Odds ratios were calculated to assess the relationship between subclinical hypothyroidism and extrathyroidal extension (ETE) after adjusting for BMI and genders. The Cancer Genome Atlas (TCGA) data were utilized for the analysis of TSHR-associated pathways, while qRT-PCR was employed to validate the expression levels of pivotal genes in the relevant signaling pathways.ResultsIn total, 13,717 PTC patients (10,769 women and 2,948 men; mean [SD] age, 42.90 [9.43] years) were included in the retrospective study. Subclinical hypothyroidism was an independent risk factor for ETE (OR adjusted, 1.168 [95% CI, 1.028–1.327]; P=0.017). In normal-weight patients, subclinical hypothyroidism was an independent risk factor for ETE (OR adjusted, 1.287 [95% CI, 1.089–1.520]; P=0.003). However, this risk was not observed in under-weight, overweight, and obese patients. Compared to females, subclinical hypothyroidism was a higher risk factor for ETE in male patients with normal body weight (OR male=2.363 vs. OR female=1.228). Subclinical hypothyroidism was found to be a significant risk factor for ETE in the subgroup of patients younger than 38 years old (OR1 adjusted, 1.382 [95% CI, 1.032–1.852], P=0.030). The findings from Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed the involvement of the autophagy signaling pathway in TSHR/ETE/EMT regulation. Moreover, the gene expression levels demonstrated a concentration-dependent relationship between TSH intervention levels and the expression of key genes in the autophagy pathway of thyroid cancer cells.ConclusionSubclinical hypothyroidism was an independent risk factor for ETE in patients with PTC. This association was particularly significant in normal-weight and younger patients. The risk of ETE associated with subclinical hypothyroidism was higher in males compared to females. Our study indicates a potential involvement of the autophagy pathway in regulating the ETE phenotype in thyroid cancer, specifically in the context of subclinical hypothyroidism

Hyperoxalemia Leads to Oxidative Stress in Endothelial Cells and Mice with Chronic Kidney Disease

Introduction: Cardiovascular disease is the most common cause of morbidity and mortality in patients with ESRD. In addition to phosphate overload, oxalate, a common uremic toxin, is also involved in vascular calcification in patients with ESRD. The present study investigated the role and mechanism of hyperoxalemia in vascular calcification in mice with uremia. Methods: A uremic atherosclerosis (UA) model was established by left renal excision and right renal electrocoagulation in apoE−/− mice to investigate the relationship between oxalate loading and vascular calcification. After 12 weeks, serum and vascular levels of oxalate, vascular calcification, inflammatory factors (TNF-α and IL-6), oxidative stress markers (malondialdehyde [MDA], and advanced oxidation protein products [AOPP]) were assessed in UA mice. The oral oxalate-degrading microbe Oxalobacter formigenes (O. formigenes) was used to evaluate the effect of a reduction in oxalate levels on vascular calcification. The mechanism underlying the effect of oxalate loading on vascular calcification was assessed in cultured human aortic endothelial cells (HAECs) and human aortic smooth muscle cells (HASMCs). Results: Serum oxalate levels were significantly increased in UA mice. Compared to the control mice, UA mice developed more areas of aortic calcification and showed significant increases in aortic oxalate levels and serum levels of oxidative stress markers and inflammatory factors. The correlation analysis showed that serum oxalate levels were positively correlated with the vascular oxalate levels and serum MDA, AOPP, and TNF-α levels, and negatively correlated with superoxide dismutase activity. The O. formigenes intervention decreased serum and vascular oxalate levels, while did not improve vascular calcification significantly. In addition, systemic inflammation and oxidative stress were also improved in the O. formigenes group. In vitro, high concentrations of oxalate dose-dependently increased oxidative stress and inflammatory factor expression in HAECs, but not in HASMCs. Conclusions: Our results indicated that hyperoxalemia led to the systemic inflammation and the activation of oxidative stress. The reduction in oxalate levels by O. formigenes might be a promising treatment for the prevention of oxalate deposition in calcified areas of patients with ESRD

LncRNA FOXD2-AS1 Functions as a Competing Endogenous RNA to Regulate TERT Expression by Sponging miR-7-5p in Thyroid Cancer

Long non-coding RNA FOXD2 Adjacent Opposite Strand RNA 1 (FOXD2-AS1) has been widely reported to be implicated in the progression and recurrence of several cancers. The clinical significance and functional role of FOXD2-AS1 in thyroid carcinoma remain unknown. FOXD2-AS1 expression was evaluated by analyzing thyroid cancer RNA sequencing dataset from The Cancer Genome Atlas (TCGA). In vitro and in vivo assays were performed to assess the biological roles of FOXD2-AS1 in thyroid cancer cells. Western blot, luciferase, immunoprecipitation (IP), and RNA immunoprecipitation (RIP) assays were used to identify the underlying miRNA and mRNA target mediating the biological roles of FOXD2-AS1 in thyroid cancer cells. FOXD2-AS1 was upregulated in thyroid carcinoma tissues and cells. High expression of FOXD2-AS1 significantly correlated with clinical stage, recurrence of thyroid carcinoma. Silencing FOXD2-AS1 inhibited cancer stem cell-like phenotypes and attenuates the anoikis resistance in vitro. Downregulating FOXD2-AS1 represses the tumorigenesis of thyroid carcinoma cells in vivo. FOXD2-AS1 acts as a competitive endogenous RNA (ceRNA) for miR-7-5p, up-regulating the expression of telomerase reverse transcriptase (TERT), which further promotes the cancer stem cells features and anoikis resistance in thyroid cancer cells. Our findings indicate that FOXD2-AS1 functions as an oncogenic regulator in the development of thyroid cancer, contributing to early recurrence of thyroid cancer

Co-infusion of haplo-identical CD19-chimeric antigen receptor T cells and stem cells achieved full donor engraftment in refractory acute lymphoblastic leukemia

Abstract Background Elderly patients with relapsed and refractory acute lymphoblastic leukemia (ALL) have poor prognosis. Autologous CD19 chimeric antigen receptor-modified T (CAR-T) cells have potentials to cure patients with B cell ALL; however, safety and efficacy of allogeneic CD19 CAR-T cells are still undetermined. Case presentation We treated a 71-year-old female with relapsed and refractory ALL who received co-infusion of haplo-identical donor-derived CD19-directed CAR-T cells and mobilized peripheral blood stem cells (PBSC) following induction chemotherapy. Undetectable minimal residual disease by flow cytometry was achieved, and full donor cell engraftment was established. The transient release of cytokines and mild fever were detected. Significantly elevated serum lactate dehydrogenase, alanine transaminase, bilirubin and glutamic-oxalacetic transaminase were observed from days 14 to 18, all of which were reversible after immunosuppressive therapy. Conclusions Our preliminary results suggest that co-infusion of haplo-identical donor-derived CAR-T cells and mobilized PBSCs may induce full donor engraftment in relapsed and refractory ALL including elderly patients, but complications related to donor cell infusions should still be cautioned. Trial registration Allogeneic CART-19 for Elderly Relapsed/Refractory CD19+ ALL. NCT0279955

ICTD: A semi-supervised cell type identification and deconvolution method for multi-omics data

We developed a novel deconvolution method, namely Inference of Cell Types and Deconvolution (ICTD) that addresses the fundamental issue of identifiability and robustness in current tissue data deconvolution problem. ICTD provides substantially new capabilities for omics data based characterization of a tissue microenvironment, including (1) maximizing the resolution in identifying resident cell and sub types that truly exists in a tissue, (2) identifying the most reliable marker genes for each cell type, which are tissue and data set specific, (3) handling the stability problem with co-linear cell types, (4) co-deconvoluting with available matched multi-omics data, and (5) inferring functional variations specific to one or several cell types. ICTD is empowered by (i) rigorously derived mathematical conditions of identifiable cell type and cell type specific functions in tissue transcriptomics data and (ii) a semi supervised approach to maximize the knowledge transfer of cell type and functional marker genes identified in single cell or bulk cell data in the analysis of tissue data, and (iii) a novel unsupervised approach to minimize the bias brought by training data. Application of ICTD on real and single cell simulated tissue data validated that the method has consistently good performance for tissue data coming from different species, tissue microenvironments, and experimental platforms. Other than the new capabilities, ICTD outperformed other state-of-the-art devolution methods on prediction accuracy, the resolution of identifiable cell, detection of unknown sub cell types, and assessment of cell type specific functions. The premise of ICTD also lies in characterizing cell-cell interactions and discovering cell types and prognostic markers that are predictive of clinical outcomes

Directional Reflective Surface Formed via Gradient-Impeding Acoustic Meta-Surfaces

Artificially designed acoustic meta-surfaces have the ability to manipulate sound energy to an extraordinary extent. Here, we report on a new type of directional reflective surface consisting of an array of sub-wavelength Helmholtz resonators with varying internal coiled path lengths, which induce a reflection phase gradient along a planar acoustic meta-surface. The acoustically reshaped reflective surface created by the gradient-impeding meta-surface yields a distinct focal line similar to a parabolic cylinder antenna, and is used for directive sound beamforming. Focused beam steering can be also obtained by repositioning the source (or receiver) off axis, i.e., displaced from the focal line. Besides flat reflective surfaces, complex surfaces such as convex or conformal shapes may be used for sound beamforming, thus facilitating easy application in sound reinforcement systems. Therefore, directional reflective surfaces have promising applications in fields such as acoustic imaging, sonic weaponry, and underwater communicationope