Unsupervised Adaptation of Polyp Segmentation Models via Coarse-to-Fine Self-Supervision

Unsupervised Domain Adaptation~(UDA) has attracted a surge of interest over the past decade but is difficult to be used in real-world applications. Considering the privacy-preservation issues and security concerns, in this work, we study a practical problem of Source-Free Domain Adaptation (SFDA), which eliminates the reliance on annotated source data. Current SFDA methods focus on extracting domain knowledge from the source-trained model but neglects the intrinsic structure of the target domain. Moreover, they typically utilize pseudo labels for self-training in the target domain, but suffer from the notorious error accumulation problem. To address these issues, we propose a new SFDA framework, called Region-to-Pixel Adaptation Network~(RPANet), which learns the region-level and pixel-level discriminative representations through coarse-to-fine self-supervision. The proposed RPANet consists of two modules, Foreground-aware Contrastive Learning (FCL) and Confidence-Calibrated Pseudo-Labeling (CCPL), which explicitly address the key challenges of ``how to distinguish'' and ``how to refine''. To be specific, FCL introduces a supervised contrastive learning paradigm in the region level to contrast different region centroids across different target images, which efficiently involves all pseudo labels while robust to noisy samples. CCPL designs a novel fusion strategy to reduce the overconfidence problem of pseudo labels by fusing two different target predictions without introducing any additional network modules. Extensive experiments on three cross-domain polyp segmentation tasks reveal that RPANet significantly outperforms state-of-the-art SFDA and UDA methods without access to source data, revealing the potential of SFDA in medical applications.Comment: Accepted by IPMI 202

Wogonoside exerts potential anti-tumor activity against bladder cancer in vivo and in vitro via regulation of GSK3β/ERK/AKT signaling pathway

Purpose: To explore the antitumor activity of wogonoside on bladder cancer, and its underlying mechanism of action. Methods: Methyl thiazolyl tetrazolium (MTT) assay was applied to evaluate the anti-proliferative activity of wogonoside (2 - 128 μM) against bladder cancer 5637 cell line at different times, and the half maximal inhibitory concentration (IC50) was measured. The antitumor activity of wogonoside (30 mg/kg, i.p.) against bladder cancer 5637 cell line was confirmed via in vivo experiments on nude mice bearing human bladder cancer 5637 cells. Additionally, western blotting assay and enzyme-linked immunosorbent assay (ELISA) were used to investigate expression levels of caspase-3, caspase-9, B cell lymphoma/leukemia-2 (Bcl-2), Bcl-2 associated X protein (Bax), phosphorylated (p)-glycogen synthase kinase (GSK)-3β, p-extracellular signal-regulated kinases (p-ERK), and p-(protein kinase B) AKT. Results: The in vitro results reveal that wogonoside has remarkable anti-proliferative activity against bladder cancer 5637 cells with IC50 of 20.59 μM, in a concentration-and time-dependent manner. Furthermore, wogonoside treatment also suppressed tumor volume of nude mice bearing bladder cancer 5637 cell (p < 0.01). The potential mechanisms seems to be mainly associated with apoptosis mediated by mitochondria via up-regulation of caspase-3, caspase-9, and Bax levels, and downregulation of Bcl-2, p-GSK-3β, p-ERK, and p-AKT. Conclusion: The results reveal that wogonoside possesses anti-tumor potentials against bladder cancer. Further translational studies are warranted to test the clinical application of this medicinal agent in bladder cancer

Baicalein and U0126 suppress bladder cancer proliferation via MAPK signaling pathway

Purpose: To investigate baicalein and 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio] butadiene (U0126)effects on human bladder cell line T24 proliferation and related mechanisms.Methods: Twenty micromoles of baicalein or 10 μM U0126 were incubated with T24 cells. Cell viability was tested by CCK8 assay. Cell cycle was evaluated by flow cytometry while cell apoptosis was detected by Annexin V/PI and TUNEL assay. MAPK signaling pathway was evaluated by real time polymerase chain reaction (RT-PCR) and western blot.Results: Baicalein and U0126 suppressed bladder cancer cell T24 proliferation by blocking cell cycle in G0~G1 phase. TUNEL and Annexin V/PI detection showed both baicalein and U0126 induced T24 cell apoptosis. Baicalein and U0126 significantly down-regulated MAPK signaling pathway related molecule activity in both mRNA and protein levels (p < 0.05).Conclusion: Baicalein and U0126 restrain bladder cancer cell proliferation and promote cell apoptosis by affecting MAPK signaling pathway. Thus, they have  potentials for use in the treatment of bladder cancer.Keywords: Bladder cancer, Baicalein, 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio] butadiene, MAPK signal pathway, Apoptosi

Trends in Prehypertension and Hypertension Risk Factors in US Adults: 1999-2012.

Prehypertension is associated with increased risk for hypertension and cardiovascular disease. Data are limited on the temporal changes in the prevalence of prehypertension and risk factors for hypertension and cardiovascular disease among US adults with prehypertension. We analyzed data from 30 958 US adults ≥20 years of age who participated in the National Health and Nutrition Examination Surveys between 1999 and 2012. Using the mean of 3 blood pressure (BP) measurements from a study examination, prehypertension was defined as systolic BP of 120 to 139 mm Hg and diastolic BP <90 mm Hg or diastolic BP of 80 to 89 mm Hg and systolic BP <140 mm Hg among participants not taking antihypertensive medication. Between 1999-2000 and 2011-2012, the percentage of US adults with prehypertension decreased from 31.2% to 28.2% (P trend=0.007). During this time period, the prevalence of several risk factors for cardiovascular disease and incident hypertension increased among US adults with prehypertension, including prediabetes (9.6% to 21.6%), diabetes mellitus (6.0% to 8.5%), overweight (33.5% to 37.3%), and obesity (30.6% to 35.2%). There was a nonstatistically significant increase in no weekly leisure-time physical activity (40.0% to 43.9%). Also, the prevalence of adhering to the Dietary Approaches to Stop Hypertension eating pattern decreased (18.4% to 11.9%). In contrast, there was a nonstatistically significant decline in current smoking (25.9% to 23.2%). In conclusion, the prevalence of prehypertension has decreased modestly since 1999-2000. Population-level approaches directed at adults with prehypertension are needed to improve risk factors to prevent hypertension and cardiovascular disease

Wogonoside exerts potential anti-tumor activity against bladder cancer in vivo and in vitro via regulation of GSK3β/ERK/AKT signaling pathway

Purpose: To explore the antitumor activity of wogonoside on bladder cancer, and its underlying mechanism of action. Methods: Methyl thiazolyl tetrazolium (MTT) assay was applied to determine the anti-proliferative activity of wogonoside (2 - 128 μM) on bladder cancer 5637 cell line at various times, and the halfmaximal inhibitory concentration (IC50) was measured. The antitumor activity of wogonoside (30 mg/kg, ip) against bladder cancer 5637 cell line was evaluated in nude mice bearing human bladder cancer 5637 cells. Additionally, western blotting and enzyme-linked immunosorbent assay (ELISA) were carried out to investigate the levels of the caspase-3, caspase-9, B cell lymphoma/leukemia-2 (Bcl-2), Bcl-2 associated X-protein (Bax), phosphorylated (p)-glycogen synthase kinase (GSK)-3β, p-extracellular signal-regulated kinases (p-ERK), and p-(protein kinase B) AKT. Results: The in vitro results revealed that wogonoside exerted anti-proliferative activity against bladder cancer 5637 cells with an IC50 of 20.59 μM (p < 0.01), in a concentration- and time-dependent manner. Furthermore, wogonoside treatment also significantly suppressed tumor volume in mice (p < 0.01). The potential mechanisms were mainly associated with apoptosis mediated by mitochondria via upregulation of caspase-3, caspase-9, and Bax levels and down-regulation of Bcl-2, p-GSK-3β, p-ERK, and p-AKT. Conclusion: The results reveal that wogonoside has remarkable anti-tumor potentials against bladder cancer. Further translational studies are warranted to test the clinical application of this medicinal agent in bladder cancer

Tell Me the Evidence? Dual Visual-Linguistic Interaction for Answer Grounding

Answer grounding aims to reveal the visual evidence for visual question answering (VQA), which entails highlighting relevant positions in the image when answering questions about images. Previous attempts typically tackle this problem using pretrained object detectors, but without the flexibility for objects not in the predefined vocabulary. However, these black-box methods solely concentrate on the linguistic generation, ignoring the visual interpretability. In this paper, we propose Dual Visual-Linguistic Interaction (DaVI), a novel unified end-to-end framework with the capability for both linguistic answering and visual grounding. DaVI innovatively introduces two visual-linguistic interaction mechanisms: 1) visual-based linguistic encoder that understands questions incorporated with visual features and produces linguistic-oriented evidence for further answer decoding, and 2) linguistic-based visual decoder that focuses visual features on the evidence-related regions for answer grounding. This way, our approach ranked the 1st place in the answer grounding track of 2022 VizWiz Grand Challenge.Comment: Accepted to CVPR 2022 VizWiz Worksho

Development and validation of a model based on immunogenic cell death related genes to predict the prognosis and immune response to bladder urothelial carcinoma

BackgroundImmunogenic cell death (ICD) has been categorized as a variant of regulated cell death that is capable of inducing an adaptive immune response. A growing body of evidence has indicated that ICD can modify the tumor immune microenvironment by releasing danger signals or damage-associated molecular patterns (DAMPs), potentially enhancing the efficacy of immunotherapy. Consequently, the identification of biomarkers associated with ICD that can classify patients based on their potential response to ICD immunotherapy would be highly advantageous. Therefore the goal of the study is to better understand and identify what patients with bladder urothelial carcinoma (BLCA) will respond to immunotherapy by analyzing ICD signatures and investigate ICD-related prognostic factors in the context of BLCA.MethodsThe data obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases regarding BLCA and normal samples was categorized based on ICD-related genes (IRGs). Specifically, we conducted an immunohistochemical (IHC) experiment to validate the expression levels of Calreticulin (CALR) in both tumor and adjacent tissues, and evaluated its prognostic significance using the Kaplan-Meier (KM) curve. Subsequently, the samples from TCGA were divided into two subtypes using consensus clustering. To obtain a more comprehensive comprehension of the biological functions, we utilized Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). The calculation of immune landscape between two subtypes was performed through ESTIMATE and CIBERSORT. Risk models were constructed using Cox and Lasso regression and their prognosis predictive ability was evaluated using nomogram, receiver operating characteristic (ROC), and calibration curves. Finally, Tumor Immune Dysfunction and Exclusion (TIDE) algorithms was utilized to predict the response to immunotherapy.ResultsA total of 34 IRGs were identified, with most of them exhibiting upregulation in BLCA samples. The expression of CALR was notably higher in BLCA compared to the adjacent tissue, and this increase was associated with an unfavorable prognosis. The differentially expressed genes (DEGs) associated with ICD were linked to various immune-related pathways. The ICD-high subtypes exhibited an immune-activated tumor microenvironment (TME) compared to the ICD-low subtypes. Utilizing three IRGs including CALR, IFNB1, and IFNG, a risk model was developed to categorize BLCA patients into high- and low-risk groups. The overall survival (OS) was considerably greater in the low-risk group compared to the high-risk group, as evidenced by both the TCGA and GEO cohorts. The risk score was identified as an independent prognostic parameter (all p < 0.001). Our model demonstrated good predictive ability (The area under the ROC curve (AUC), AUC1-year= 0.632, AUC3-year= 0.637, and AUC5-year =0.653). Ultimately, the lower risk score was associated with a more responsive immunotherapy group.ConclusionThe potential of the ICD-based risk signature to function as a marker for evaluating the prognosis and immune landscape in BLCA suggests its usefulness in identifying the suitable population for effective immunotherapy against BLCA

Digital Twin Brain: a simulation and assimilation platform for whole human brain

In this work, we present a computing platform named digital twin brain (DTB) that can simulate spiking neuronal networks of the whole human brain scale and more importantly, a personalized biological brain structure. In comparison to most brain simulations with a homogeneous global structure, we highlight that the sparseness, couplingness and heterogeneity in the sMRI, DTI and PET data of the brain has an essential impact on the efficiency of brain simulation, which is proved from the scaling experiments that the DTB of human brain simulation is communication-intensive and memory-access intensive computing systems rather than computation-intensive. We utilize a number of optimization techniques to balance and integrate the computation loads and communication traffics from the heterogeneous biological structure to the general GPU-based HPC and achieve leading simulation performance for the whole human brain-scaled spiking neuronal networks. On the other hand, the biological structure, equipped with a mesoscopic data assimilation, enables the DTB to investigate brain cognitive function by a reverse-engineering method, which is demonstrated by a digital experiment of visual evaluation on the DTB. Furthermore, we believe that the developing DTB will be a promising powerful platform for a large of research orients including brain-inspiredintelligence, rain disease medicine and brain-machine interface.Comment: 12 pages, 11 figure