Locating X-Ray Coronary Angiogram Keyframes via Long Short-Term Spatiotemporal Attention With Image-to-Patch Contrastive Learning.

Locating the start, apex and end keyframes of moving contrast agents for keyframe counting in X-ray coronary angiography (XCA) is very important for the diagnosis and treatment of cardiovascular diseases. To locate these keyframes from the class-imbalanced and boundary-agnostic foreground vessel actions that overlap complex backgrounds, we propose long short-term spatiotemporal attention by integrating a convolutional long short-term memory (CLSTM) network into a multiscale Transformer to learn the segment- and sequence-level dependencies in the consecutive-frame-based deep features. Image-to-patch contrastive learning is further embedded between the CLSTM-based long-term spatiotemporal attention and Transformer-based short-term attention modules. The imagewise contrastive module reuses the long-term attention to contrast image-level foreground/background of XCA sequence, while patchwise contrastive projection selects the random patches of backgrounds as convolution kernels to project foreground/background frames into different latent spaces. A new XCA video dataset is collected to evaluate the proposed method. The experimental results show that the proposed method achieves a mAP (mean average precision) of 72.45% and a F-score of 0.8296, considerably outperforming the state-of-the-art methods. The source code is available at https://github.com/Binjie-Qin/STA-IPCon.

LncRNA PANTR1 is Associated with Poor Prognostic and Suppresses Apoptosis in Glioma.

Glioma is the most common tumor in the central nervous system. High-grade gliomas confer a poor prognosis, being a serious health and economic burden. Current literature suggests the important role of long noncoding RNA (lncRNA) in mammals, especially in tumorigenesis of various tumors. The functions of lncRNA POU3F3 adjacent noncoding transcript 1 (PANTR1) have been investigated in hepatocellular carcinoma but remain yet unclear in gliomas. We evaluated the role of PANTR1 in glioma cells using published data from The Cancer Genome Atlas (TCGA), then validated it by ex vivo experiments. To investigate the potential cellular mechanism of different levels of PANTR1 expression in glioma cells, we used siRNA-mediated knockdown in low-grade (grade II) cell lines and GBM (grade IV) cell lines (SW1088 and SHG44, respectively). On the molecular level, low expression of PANTR1 caused significantly reduced glioma cell viability and enhanced cell death. Moreover, we identified the importance of PANTR1 expression for cell migration in both cell lines, a critical foundation for invasiveness in recurrent gliomas. In conclusion, this study provides the first evidence that PANTR1 has a relevant role in human glioma by influencing cell viability and cell death.

Corrigendum: m6A regulatory gene-mediated methylation modification in glioma survival prediction.

[This corrects the article DOI: 10.3389/fgene.2022.873764.].

High stone-free rate immediately after suctioning flexible ureteroscopy with Intelligent pressure-control in treating upper urinary tract calculi.

BACKGROUND: The retrospective observational study aimed to evaluate the safety and efficacy of suctioning flexible ureteroscopy with Intelligent pressure-control (SFUI) on treating upper urinary tract calculi in a large cohort. METHODS: Between July 2020 and August 2021, 278 patients with upper urinary tract calculi who underwent SFUI in our hospital were enrolled. Outcomes were stone-free rate (SFR) in one session and one-month after SFUI treatment, and complications scored by the Clavien-Dindo classification. RESULTS: A total of 310 kidneys underwent SFUI were included. The median surgery time was 75 min (ranged 60-110 min). One session and one-month SFRs were 80.65% and 82.26%, respectively. The one-session SFR was ≧ 87% in patients with Guy's stone score of Grade I among stone size < 40 mm. Risk factors for unsuccessful stone-free in one session were stone history (adjusted odds ratio (aOR): 2.39, 95% confidence interval (CI): 1.21-4.73), stone size of 40-49 mm (aOR: 4.37, 95% CI: 1.16-16.45), Guy's stone score ≧ Grade II (Grade II, aOR: 3.54, 95% CI: 1.18-10.59; Grade III, aOR: 10.95, 95% CI: 2.65-45.25). The incidence of Clavien-Dindo grade II-III complication was 3.26%. Complication is associated with Guy's stone score III (aOR: 22.36, 95% CI: 1.81-276.36). CONCLUSION: SFUI shows good safety and efficiency on treating upper urinary tract calculi. Patients with stone size < 40 mm or Guy's stone score of Grade I have a high chance to reach stone-free after SFUI treatment.

m6A Regulatory Gene-Mediated Methylation Modification in Glioma Survival Prediction.

The median survival of patients with gliomas is relatively short. To investigate the epigenetic mechanisms associated with poor survival, we analyzed publicly available datasets from patients with glioma. This analysis revealed 12 prognosis-related m6A regulatory genes that may be responsible for poor prognosis. These genes may be involved in genomic changes inherent to oxidative phosphorylation, adipogenesis, hedgehog signaling, and Myc signaling. We reconstructed a risk model with univariate and multivariate Cox analyses and identified older age and the m6A risk score as independent risk factors for predicting the prognosis of glioma patients, which is associated with glioma immune infiltration. In conclusion, m6A regulatory genes may serve as both reliable biomarkers and potential targets to increase the chance of survival of patients with glioma.

Robust PCA Unrolling Network for Super-Resolution Vessel Extraction in X-Ray Coronary Angiography.

Although robust PCA has been increasingly adopted to extract vessels from X-ray coronary angiography (XCA) images, challenging problems such as inefficient vessel-sparsity modelling, noisy and dynamic background artefacts, and high computational cost still remain unsolved. Therefore, we propose a novel robust PCA unrolling network with sparse feature selection for super-resolution XCA vessel imaging. Being embedded within a patch-wise spatiotemporal super-resolution framework that is built upon a pooling layer and a convolutional long short-term memory network, the proposed network can not only gradually prune complex vessel-like artefacts and noisy backgrounds in XCA during network training but also iteratively learn and select the high-level spatiotemporal semantic information of moving contrast agents flowing in the XCA-imaged vessels. The experimental results show that the proposed method significantly outperforms state-of-the-art methods, especially in the imaging of the vessel network and its distal vessels, by restoring the intensity and geometry profiles of heterogeneous vessels against complex and dynamic backgrounds. The source code is available at https://github.com/Binjie-Qin/RPCA-UNet.

Sequential vessel segmentation via deep channel attention network.

Accurately segmenting contrast-filled vessels from X-ray coronary angiography (XCA) image sequence is an essential step for the diagnosis and therapy of coronary artery disease. However, developing automatic vessel segmentation is particularly challenging due to the overlapping structures, low contrast and the presence of complex and dynamic background artifacts in XCA images. This paper develops a novel encoder-decoder deep network architecture which exploits the several contextual frames of 2D+t sequential images in a sliding window centered at current frame to segment 2D vessel masks from the current frame. The architecture is equipped with temporal-spatial feature extraction in encoder stage, feature fusion in skip connection layers and channel attention mechanism in decoder stage. In the encoder stage, a series of 3D convolutional layers are employed to hierarchically extract temporal-spatial features. Skip connection layers subsequently fuse the temporal-spatial feature maps and deliver them to the corresponding decoder stages. To efficiently discriminate vessel features from the complex and noisy backgrounds in the XCA images, the decoder stage effectively utilizes channel attention blocks to refine the intermediate feature maps from skip connection layers for subsequently decoding the refined features in 2D ways to produce the segmented vessel masks. Furthermore, Dice loss function is implemented to train the proposed deep network in order to tackle the class imbalance problem in the XCA data due to the wide distribution of complex background artifacts. Extensive experiments by comparing our method with other state-of-the-art algorithms demonstrate the proposed method's superior performance over other methods in terms of the quantitative metrics and visual validation. To facilitate the reproductive research in XCA community, we publicly release our dataset and source codes at https://github.com/Binjie-Qin/SVS-net.

Accurate vessel extraction via tensor completion of background layer in X-ray coronary angiograms.

This paper proposes an effective method for accurately recovering vessel structures and intensity information from the X-ray coronary angiography (XCA) images of moving organs or tissues. Specifically, a global logarithm transformation of XCA images is implemented to fit the X-ray attenuation sum model of vessel/background layers into a low-rank, sparse decomposition model for vessel/background separation. The contrast-filled vessel structures are extracted by distinguishing the vessels from the low-rank backgrounds by using a robust principal component analysis and by constructing a vessel mask via Radon-like feature filtering plus spatially adaptive thresholding. Subsequently, the low-rankness and inter-frame spatio-temporal connectivity in the complex and noisy backgrounds are used to recover the vessel-masked background regions using tensor completion of all other background regions, while the twist tensor nuclear norm is minimized to complete the background layers. Finally, the method is able to accurately extract vessels' intensities from the noisy XCA data by subtracting the completed background layers from the overall XCA images. We evaluated the vessel visibility of resulting images on real X-ray angiography data and evaluated the accuracy of vessel intensity recovery on synthetic data. Experiment results show the superiority of the proposed method over the state-of-the-art methods.

Texture Variation Adaptive Image Denoising With Nonlocal PCA.

Image textures, as a kind of local variations, provide important information for the human visual system. Many image textures, especially the small-scale or stochastic textures, are rich in high-frequency variations, and are difficult to be preserved. Current state-of-the-art denoising algorithms typically adopt a nonlocal approach consisting of image patch grouping and group-wise denoising filtering. To achieve a better image denoising while preserving the variations in texture, we first adaptively group high correlated image patches with the same kinds of texture elements (texels) via an adaptive clustering method. This adaptive clustering method is applied in an over-clustering-and-iterative-merging approach, where its noise robustness is improved with a custom merging threshold relating to the noise level and cluster size. For texture-preserving denoising of each cluster, considering that the variations in texture are captured and wrapped in not only the between-dimension energy variations but also the within-dimension variations of PCA transform coefficients, we further propose a PCA-transform-domain variation adaptive filtering method to preserve the local variations in textures. Experiments on natural images show the superiority of the proposed transform-domain variation adaptive filtering to traditional PCA-based hard or soft threshold filtering. As a whole, the proposed denoising method achieves a favorable texture-preserving performance both quantitatively and visually, especially for irregular textures, which is further verified in camera raw image denoising.

The role of TSG-6 and uroplakin III in bladder pain syndrome/ interstitial cystitis in rats and humans.

OBJECTIVES: We investigated the relationship between the expression of tumor necrosis factor-inducible gene 6 (TSG-6) with inflammation and integrity of the bladder epithelium in the bladder tissues of patients with bladder pain syndrome/interstitial cystitis (BPS/IC) and the mechanism of action using a rat model of BPS/IC. MATERIALS AND METHODS: Expression of TSG-6 and uroplakin III was determined by immuno- histochemistry of bladder biopsy samples from control human subjects and patients with verified BPS/IC. Our rat model of BPS/IC was employed to measure the perfusion of bladders with hyaluronidase, and assessment of the effect of TSG-6 administration on disease progression. Treatment effects were assessed by measurement of metabolic characteristics, RT-PCR of TGR-6 and interleukin-6, bladder histomorphology, and immunohistochemistry of TGR-6 and uroplakin III. RESULTS: The bladders of patients with BPS/IC had lower expression of uroplakin III and higher expression of TSG-6 than controls. Rats treated with hyaluronidase for 1 week developed the typical signs and symptoms of BPS/IC, and rats treated with hyaluronidase for 4 weeks had more serious disease. Administration of TSG-6 reversed the effects of hyaluronidase and protected against disease progression. CONCLUSION: Our results indicate that TSG-6 plays an important role in maintaining the integrity of the bladder epithelial barrier.

Curcumin prevents the non-alcoholic fatty hepatitis via mitochondria protection and apoptosis reduction.

BACKGROUND: Non-alcoholic fatty hepatitis (NASH) is highly prevalent, mitochondria damage is the main pathophysiological characteristic of NASH. However, treatment for mitochondria damage is rarely reported. METHODS: NASH model was established in rats, the protective effects of curcumin were evaluated by histological observation; structure and function assessments of mitochondria; and apoptotic genes expression. RESULTS: NASH rats treated with curcumin displayed relatively slight liver damage when compared with NASH livers. The average mitochondrial length and width of NASH (12.0 ± 3.2 and 5.1 ± 1.1 micrometers) were significantly longer than that of normal (6.2 ± 2.1 and 2.1 ± 1.5 micrometers) and NASH treated with curcumin (7.4 ± 1.2 and 3.2 ± 1.5 micrometers) rats. The average malondialdehyde (MDA) and 4-hydroxy nonyl alcohol (HNE) levels in liver homogenates of NASH rats (4.23 ± 0.22 and 19.23 ± 2.3 nmol/Ml) were significantly higher than these in normal (1.32 ± 0.12 and 3.52 ± 0.43 nmol/mL) and NASH treated with curcumin (1.74 ± 0.11 and 4.66 ± 0.99 nmol/mL) rats. The expression levels of CytC, Casp3 and Casp8 of the NASH livers were significantly higher than normal and NASH treated with curcumin rats livers. CONCLUSION: Our data demonstrated that curcumin prevents the NASH by mitochondria protection and apoptosis reduction and provided a possible novel treatment for NASH.

Current status of diagnosis and treatment of bladder cancer in China - Analyses of Chinese Bladder Cancer Consortium database.

OBJECTIVE: To investigate current status of diagnosis and treatment of bladder cancer in China. METHODS: A database was generated by Chinese Bladder Cancer Consortium (CBCC). From January 2007 to December 2012, 14,260 cases from 44 CBCC centers were included. Data of diagnosis, treatment and pathology were collected. RESULTS: The average age was 63.5 year-old and most patients were male (84.3%). The most common histologic types were urothelial carcinoma (91.4%), adenocarcinoma (1.8%), and squamous carcinoma (1.9%). According to 1973 and 2004 WHO grading system, 42.0%, 41.0%, and 17.0% of patients were grade 1, 2, and 3, and 16.0%, 48.7%, and 35.3% of patients were papillary urothelial neoplasms of low malignant potential, low, and high grade, respectively. Non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC) were 25.2% and 74.1%, respectively (0.8% not clear). Carcinoma in situ was only 2.4%. Most patients were diagnosed by white-light cystoscopy with biopsy (74.3%). Fluorescence and narrow band imaging cystoscopy had additional detection rate of 1.0% and 4.0%, respectively. Diagnostic transurethral resection (TUR) provided detection rate of 16.9%. Most NMIBCs were treated with TUR (89.2%). After initial TUR, 2.6% accepted second TUR, and 45.7%, 69.9%, and 58.7% accepted immediate, induced, and maintenance chemotherapy instillation, respectively. Most MIBCs were treated with radical cystectomy (RC, 59.7%). Laparoscopic RCs were 35.1%, while open RC 63.4%. Extended and standard pelvic lymph node dissection were 7% and 66%, respectively. Three most common urinary diversions were orthotopic neobladder (44%), ileal conduit (31%), and ureterocutaneostomy (23%). Only 2.3% of patients accepted neo-adjuvant chemotherapy and only 18% of T3 and T4 patients accepted adjuvant chemotherapy. CONCLUSION: Disease characteristics are similar to international reports, while differences of diagnosis and treatment exist. This study can provide evidences for revisions of the guideline on bladder cancer in China.

Intercellular transfer of P-glycoprotein from the drug resistant human bladder cancer cell line BIU-87 does not require cell-to-cell contact.

PURPOSE: The efflux activity of transmembrane P-glycoprotein prevents various therapeutic drugs from reaching lethal concentrations in cancer cells, resulting in multidrug resistance. We investigated whether drug resistant bladder cancer cells could transfer functional P-glycoprotein to sensitive parental cells. MATERIALS AND METHODS: Drug sensitive BIU-87 bladder cancer cells were co-cultured for 48 hours with BIU-87/ADM, a doxorubicin resistant derivative of the same cell line, in a Transwell® system that prevented cell-to-cell contact. The presence of P-glycoprotein in recipient cell membranes was established using fluorescein isothiocyanate, laser scanning confocal microscopy and Western blot. P-glycoprotein mRNA levels were compared between cell types. Rhodamine 123 efflux assay was done to confirm that P-glycoprotein was biologically active. RESULTS: The amount of P-glycoprotein protein in BIU-87 cells co-cultured with BIU-87/ADM was significantly higher than in BIU-87 cells (0.44 vs 0.25) and BIU-87/H33342 cells (0.44 vs 0.26, each p <0.001), indicating P-glycoprotein transfer. P-glycoprotein mRNA expression was significantly higher in BIU-87/ADM cells than in co-cultured BIU-87 cells (1.28 vs 0.30), BIU-87/H33342 (0.28) and BIU-87 cells (0.25, each p <0.001), ruling out a genetic mechanism. After 30 minutes of efflux, rhodamine 123 fluorescence intensity was significantly lower in BIU-87/ADM cells (5.55 vs 51.45, p = 0.004) and co-cultured BIU-87 cells than in BIU-87 cells (14.22 vs 51.45, p <0.001), indicating that P-glycoprotein was functional. CONCLUSIONS: Bladder cancer cells can acquire functional P-glycoprotein through a nongenetic mechanism that does not require direct cell contact. This mechanism is consistent with a microparticle mediated process.

Expression and functional role of Cdx2 in intestinal metaplasia of cystitis glandularis.

PURPOSE: Cdx2 is an essential transcription factor in intestinal epithelial cell differentiation and proliferation. However, to our knowledge the expression and role of Cdx2 in the development of intestinal cystitis glandularis, a metaplastic lesion induced by chronic inflammation, remained to be explored. MATERIALS AND METHODS: Real-time polymerase chain reaction was used to examine Cdx2, LI-cadherin and villin expression in typical and intestinal cystitis glandularis, and normal bladder tissue. Cdx2 cDNA was subcloned to the retroviral vector pLNCX2 for subsequent transfection into human bladder urothelium cells and rat bladder urothelium. Cdx2 mRNA and protein levels, and cell morphology and proliferation were assessed after transfection using real-time polymerase chain reaction, phase contrast microscopy, transmission electron microscopy and MTT assay, respectively. RESULTS: Higher mRNA levels of Cdx2, villin and LI-cadherin were detected in intestinal cystitis glandularis compared to normal bladder and typical cystitis glandularis. Only Cdx2 groups attained statistical significance (p <0.001). Retroviral over expression of Cdx2 resulted in increased mRNA and protein expression of Cdx2 as well as villin and LI-cadherin levels, and increased cell proliferation. A distinct change in cellular morphology, in which cells resembled intestinal-like cells, was also observed in vitro and in vivo. CONCLUSIONS: Cdx2 may have a critical role in regulating intestinal metaplasia in cystitis glandularis. Further studies are planned to assess the potential of using Cdx2 as a marker and therapeutic target for cystitis glandularis.

Interleukin-6 levels in female rats with protamine sulfate-induced chronic cystitis treated with hyaluronic acid.

OBJECTIVES: To measure interleukin-6 levels in a protamine sulfate-induced chronic cystitis rat model treated with hyaluronic acid, and to study the correlation among interleukin-6, bladder inflammatory degree and voiding frequency. METHODS: A chronic cystitis model was created in female rats by using long-term intermittent intravesical protamine sulfate (0.5 mL, 30 mg/mL). Then, hyaluronic acid (0.5 mL, 0.8 mg/mL) was also instilled intravesically in the rats. Interleukin-6 levels were analyzed with immunohistochemistry, real-time reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was carried out to examine bladder inflammatory degree based on a four-point scoring system (from 0 - none to 3 - severe). Voiding patterns were investigated by cystometrography. RESULTS: According to cystometrography, protamine sulfate-induced rats had significantly shorter intercontraction intervals and less bladder capacity (P < 0.001). The bladder tissue of the rats showed severe chronic inflammation. Immunohistochemistry, reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay showed significantly higher expression of interleukin-6 (P < 0.001). After intravesical administration of hyaluronic acid, both intercontraction intervals and bladder capacity increased significantly (P < 0.001), whereas both bladder inflammatory degree and interleukin-6 levels decreased significantly (P < 0.001). Furthermore, there was a strong correlation between interleukin-6 levels and inflammatory degree (r = 0.727, P < 0.001), and also between interleukin-6 levels and voiding frequency (r = -0.761, P < 0.001). CONCLUSIONS: Intravesical administration of hyaluronic acid decreases interleukin-6 levels, as well as the severity of bladder inflammation and voiding frequency in a rat model of chronic cystitis. Interleukin-6 levels closely correlate with the inflammatory degree and voiding frequency. Thus, they can be regarded as an assessment measure of therapeutic impact.

Reducing Poisson noise and baseline drift in X-ray spectral images with bootstrap Poisson regression and robust nonparametric regression.

X-ray spectral imaging provides quantitative imaging of trace elements in a biological sample with high sensitivity. We propose a novel algorithm to promote the signal-to-noise ratio (SNR) of x-ray spectral images that have low photon counts. Firstly, we estimate the image data area that belongs to the homogeneous parts through confidence interval testing. Then, we apply the Poisson regression through its maximum likelihood estimation on this area to estimate the true photon counts from the Poisson noise corrupted data. Unlike other denoising methods based on regression analysis, we use the bootstrap resampling method to ensure the accuracy of regression estimation. Finally, we use a robust local nonparametric regression method to estimate the baseline and subsequently subtract it from the x-ray spectral data to further improve the SNR of the data. Experiments on several real samples show that the proposed method performs better than some state-of-the-art approaches to ensure accuracy and precision for quantitative analysis of the different trace elements in a standard reference biological sample.

Intravesical hyaluronic acid and alkalinized lidocaine for the treatment of severe painful bladder syndrome/interstitial cystitis.

INTRODUCTION AND HYPOTHESIS: Intravesical instillation of hyaluronic acid (HA) may restore the integrity of glycosaminoglycan layer in patients with painful bladder syndrome/interstitial cystitis (PBS/IC), and the benefit may be improved with addition of alkalinized lidocaine (AL). METHODS: 48 women with severe PBS/IC who failed oral medications were enrolled and divided into one trial and two control groups. The trial group received intravesical 40 mg HA, 10 ml of 2 % lidocaine and 5 ml of 8.4 % sodium bicarbonate on a weekly basis for 8 weeks and then monthly for 4 months with a subsequent follow-up of 24 weeks, while the two control groups received 40 mg HA and mixture of 10 ml of 2 % lidocaine and 5 ml of 8.4%sodium bicarbonate respectively following the same procedure. Response to therapy was evaluated by Global Response Assessment, voids per day, Visual Analogue Scale for pain, frequency and urgency, O'leary-Sant Interstitial Cystitis Symptom Index and Problem Index, cystoscopy and bladder capacity. RESULTS: Overall 45 patients finished this study protocol. The HA + AL group and the AL group showed significant improvement at week 2 (P < 0.01), while the HA group began to show effect at week 4 (P < 0.01). There was no improvement in the AL group at week 24 and these patients quitted the study without follow up. Contrarily, the HA + AL and HA group kept on improving till the end of the study without significant difference between the two groups. CONCLUSIONS: Intravesical instillation of HA and AL may provide both immediate and sustained relief of symptoms in severe PBS/IC in this preliminary study.