miR-497 target gene regulatory network in angiosarcoma.

Angiosarcoma is a vascular sarcoma that is highly aggressive and metastatic. Due to its rarity, treatment options for patients are limited, therefore more research is needed to identify possible therapeutic vulnerabilities. We previously found that conditional deletion of Dicer1 drives angiosarcoma development in mice. Given the role of DICER1 in canonical microRNA (miRNA) biogenesis, this suggests that miRNA loss is important in angiosarcoma development. After testing miRNAs previously suggested to have a tumor-suppressive role in angiosarcoma, microRNA-497-5p (miR-497) suppressed cell viability most significantly. We also found that miR-497 overexpression led to significantly reduced cell migration and tumor formation. To understand the mechanism of miR-497 in tumor suppression, we identified clinically relevant target genes using a combination of RNA-sequencing data in an angiosarcoma cell line, expression data from angiosarcoma patients, and target prediction algorithms. We validated miR-497 direct regulation of CCND2, CDK6, and VAT1. One of these genes, VAT1, is an understudied protein that has been suggested to promote cell migration and metastasis in other cancers. Indeed, we find that pharmacologic inhibition of VAT1 with the natural product Neocarzilin A reduces angiosarcoma migration. Implications: This work supports the potent tumor-suppressive abilities of miR-497 in angiosarcoma, providing evidence for its potential as a therapeutic, and provides insight into the mechanisms of tumor suppression through analysis of the target gene regulatory network of miR-497.

Target gene regulatory network of miR-497 in angiosarcoma.

Angiosarcoma (AS) is a vascular sarcoma that is highly aggressive and metastatic. Due to its rarity, treatment options for patients are limited, therefore more research is needed to identify possible therapeutic vulnerabilities. We previously found that conditional deletion of Dicer1 drives AS development in mice. Given the role of DICER1 in canonical microRNA (miRNA) biogenesis, this suggests that miRNA loss is important in AS development. After testing miRNAs previously suggested to have a tumor-suppressive role in AS, microRNA-497-5p (miR-497) suppressed cell viability most significantly. We also found that miR-497 overexpression led to significantly reduced cell migration and tumor formation. To understand the mechanism of miR-497 in tumor suppression, we identified clinically relevant target genes using a combination of RNA-sequencing data in an AS cell line, expression data from AS patients, and target prediction algorithms. We validated miR-497 direct regulation of CCND2, CDK6, and VAT1. One of these genes, VAT1, is an understudied protein that has been suggested to promote cell migration and metastasis in other cancers. Indeed, we find that pharmacologic inhibition of VAT1 with the natural product Neocarzilin A reduces AS migration. This work provides insight into the mechanisms of miR-497 and its target genes in AS pathogenesis.

Prognostic value of neutrophil-lymphocyte ratio and lactate dehydrogenase in melanoma patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) showed promising therapeutic efficacy on melanoma. Neutrophil-to-lymphocyte ratio (NLR) and serum lactate dehydrogenase (LDH) showed predictive values on prognosis of various tumors, but not on melanoma yet. This meta-analysis was conducted to investigate the prognostic role of NLR and LDH levels in melanoma treated with ICIs. METHODS: A search was conducted for all reports published till March 2020 in PubMed, Web of Science, Cochrane Library, EMBASE, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP). Studies were included if they investigated the association between pretreatment NLR/LDH and prognosis in melanoma patients treated with ICIs. Subgroup analysis, publication bias, and meta-regression were conducted to investigate heterogeneity. RESULTS: A total of 6817 melanoma patients were included. Overall, high pretreatment NLR and LDH were associated with poor overall survival (OS) (P < .001) and PFS (P < .001). Subgroup analyses revealed that elevated NLR and LDH levels were associated with poor OS and PFS in patients treated with anti-CTLA-4 or anti-PD-1/PD-L1 alone. NLR level was superior in predicting OS if compared with LDH level in patients treated with anti-PD-1/PD-L1 + anti-CTLA-4. In subgroup analysis stratified by cutoff value, high NLR level was associated with poor OS and PFS regardless of cutoff value, but LDH works when cutoff value = upper normal limit (UNL). The predictive value of NLR and LDH levels on OS and PFS was partially compromised in the Asian populations, compared with the Western countries. CONCLUSION: Blood NLR and LDH levels showed great potential to be used as early prognostic biomarkers in melanoma patients treated with ICIs.

Towards Disentangling Latent Space for Unsupervised Semantic Face Editing.

Facial attributes in StyleGAN generated images are entangled in the latent space which makes it very difficult to independently control a specific attribute without affecting the others. Supervised attribute editing requires annotated training data which is difficult to obtain and limits the editable attributes to those with labels. Therefore, unsupervised attribute editing in an disentangled latent space is key to performing neat and versatile semantic face editing. In this paper, we present a new technique termed Structure-Texture Independent Architecture with Weight Decomposition and Orthogonal Regularization (STIA-WO) to disentangle the latent space for unsupervised semantic face editing. By applying STIA-WO to GAN, we have developed a StyleGAN termed STGAN-WO which performs weight decomposition through utilizing the style vector to construct a fully controllable weight matrix to regulate image synthesis, and employs orthogonal regularization to ensure each entry of the style vector only controls one independent feature matrix. To further disentangle the facial attributes, STGAN-WO introduces a structure-texture independent architecture which utilizes two independently and identically distributed (i.i.d.) latent vectors to control the synthesis of the texture and structure components in a disentangled way. Unsupervised semantic editing is achieved by moving the latent code in the coarse layers along its orthogonal directions to change texture related attributes or changing the latent code in the fine layers to manipulate structure related ones. We present experimental results which show that our new STGAN-WO can achieve better attribute editing than state of the art methods.

The combination of transcatheter arterial chemoembolisation (TACE) and thermal ablation versus TACE alone for hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma is the sixth most common cancer worldwide. Hepatic resection is regarded as the curative therapy for hepatocellular carcinoma. However, only about 20% of people with hepatocellular carcinoma are candidates for resection, which highlights the importance of effective nonsurgical therapies. Until now, transcatheter arterial chemoembolisation (TACE) is the most common palliative therapy for hepatocellular carcinoma, but its clinical benefits remain unsatisfactory. During recent years, some studies have reported that the combination of TACE plus thermal ablation can confer a more favourable prognosis than TACE alone. However, clear and compelling evidence to prove the beneficial or harmful effects of the combination of TACE and thermal ablation therapy is lacking. OBJECTIVES: To assess the beneficial and harmful effects of the combination of thermal ablation with TACE versus TACE alone in people with hepatocellular carcinoma. SEARCH METHODS: We performed searches in the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials in the Cochrane Library, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index-Science. We endeavoured to identify relevant randomised clinical trials also in the China National Knowledge Infrastructure (CNKI) and Wanfang databases. We searched trial registration websites for ongoing studies. We also handsearched grey literature sources. The date of last search was 22 December 2020. SELECTION CRITERIA: We planned to include all randomised clinical trials comparing the combination of TACE plus thermal ablation versus TACE alone for hepatocellular carcinoma, no matter the language, year of publication, publication status, and reported outcomes. DATA COLLECTION AND ANALYSIS: We planned to use standard methodological procedures expected by Cochrane. We planned to calculate risk ratios (RRs) with the corresponding 95% confidence intervals (CIs). For time-to-event variables, we planned to use the methods of survival analysis and express the intervention effect as a hazard ratio (HR) with 95% Cl. If the log HR and the variance were not directly reported in reports, we planned to calculate them indirectly, following methods for incorporating summary time-to-event data into meta-analysis. We planned to assess the risk of bias of the included studies using the RoB 2 tool. We planned to assess the certainty of evidence with GRADE and present the evidence in a summary of findings table. MAIN RESULTS: Out of 2224 records retrieved with the searches, we considered 135 records eligible for full-text screening. We excluded 21 of these records because the interventions used were outside the scope of our review or the studies were not randomised clinical trials. We listed the remaining 114 records, reporting on 114 studies, under studies awaiting classification because we could not be sure that these were randomised clinical trials from the information in the study paper. We could not obtain information on the registration of the study protocol for any of the 114 studies. We could not obtain information on study approval by regional research ethics committees, either from the study authors or through our own searches of trial registries. Corresponding authors did not respond to our enquiries about the design and conduct of the studies, except for one from whom we did not receive a satisfactory response. We also raised awareness of our concerns to editors of the journals that published the 114 studies, and we did not hear back with useful information. Moreover, there seemed to be inappropriate inclusion of trial participants, based on cancer stage and severity of liver disease, who should have obtained other interventions according to guidelines from learned societies. Accordingly, we found no confirmed randomised clinical trials evaluating the combination of TACE plus thermal ablation versus TACE alone for people with hepatocellular carcinoma for inclusion in our review. We identified five ongoing trials, by handsearching in clinical trial websites. AUTHORS' CONCLUSIONS: We could not find for inclusion any confirmed randomised clinical trials assessing the beneficial or harmful effects of the combination of TACE plus thermal ablation versus TACE alone in people with hepatocellular carcinoma. Therefore, our results did not show or reject the efficiency of the combination of TACE plus thermal ablation versus TACE alone for people with hepatocellular carcinoma. We need trials that compare the beneficial and harmful effects of the combination of TACE plus thermal ablation versus TACE alone in people with hepatocellular carcinoma, not eligible for treatments with curative intent (liver transplantation, ablation surgical resection) and who have sufficient liver reserve, as assessed by the Child Pugh score, and who do not have extrahepatic metastases. Therefore, future trial participants must be classified at Barcelona Clinic Liver Cancer Stage B (intermediate stage) (BCLC-B) or an equivalent, with other staging systems.

Targeted up-regulation of Drp1 in dorsal horn attenuates neuropathic pain hypersensitivity by increasing mitochondrial fission.

Mitochondria play an essential role in pathophysiology of both inflammatory and neuropathic pain (NP), but the mechanisms are not yet clear. Dynamin-related protein 1 (Drp1) is broadly expressed in the central nervous system and plays a role in the induction of mitochondrial fission process. Spared nerve injury (SNI), due to the dysfunction of the neurons within the spinal dorsal horn (SDH), is the most common NP model. We explored the neuroprotective role of Drp1 within SDH in SNI. SNI mice showed pain behavior and anxiety-like behavior, which was associated with elevation of Drp1, as well as increased density of mitochondria in SDH. Ultrastructural analysis showed SNI induced damaged mitochondria into smaller perimeter and area, tending to be circular. Characteristics of vacuole in the mitochondria further showed SNI induced the increased number of vacuole, widened vac-perimeter and vac-area. Stable overexpression of Drp1 via AAV under the control of the Drp1 promoter by intraspinal injection (Drp1 OE) attenuated abnormal gait and alleviated pain hypersensitivity of SNI mice. Mitochondrial ultrastructure analysis showed that the increased density of mitochondria induced by SNI was recovered by Drp1 OE which, however, did not change mitochondrial morphology and vacuole parameters within SDH. Contrary to Drp1 OE, down-regulation of Drp1 in the SDH by AAV-Drp1 shRNA (Drp1 RNAi) did not alter painful behavior induced by SNI. Ultrastructural analysis showed the treatment by combination of SNI and Drp1 RNAi (SNI + Drp1 RNAi) amplified the damages of mitochondria with the decreased distribution density, increased perimeter and area, as well as larger circularity tending to be more circular. Vacuole data showed SNI + Drp1 RNAi increased vacuole density, perimeter and area within the SDH mitochondria. Our results illustrate that mitochondria within the SDH are sensitive to NP, and targeted mitochondrial Drp1 overexpression attenuates pain hypersensitivity. Drp1 offers a novel therapeutic target for pain treatment.

Gene Polymorphism of MUC15, MMP14, BRAF, and COL1A1 Is Associated with Capsule Formation in Hepatocellular Carcinoma.

Background: The presence of a capsule is an important prognostic factor in hepatocellular carcinoma (HCC). Capsule formation is affected by tumor-host interaction, which may include collagen deposition and extracellular matrix (ECM) degradation. Purpose: This study aimed to examine whether single-nucleotide polymorphisms (SNPs) in the genes for COL1A1 MUC15, MMP14, CD97, SMYD3, BRAF, and transforming growth factor beta 1 (TGF-ß) are related to capsule formation. Methods: We prospectively recruited and analyzed 185 patients with HCC with or without a capsule between 2019 and 2020. The SNPs involved were analyzed by polymerase chain reaction. Differences in the allele and genotype frequency between the cases and controls were evaluated using the chi-square test. Odds ratios and 95% confidence intervals were calculated by logistic regression analysis with adjustment for age and sex. Stratification analyses were also performed with preselected variables. Results: The single-locus analysis showed that the presence of a capsule was significantly associated with five SNPs : MUC15 rs17309195 (P=0.01), rs12271124 (P= 0.02), rs10430847 (P=0.04), MMP14 rs17884816 (P=0.01), and BRAF rs74512895 (P=0.03). Adjusted logistic regression revealed that the decreased capsule formation was statistically significantly associated with BRAF rs76603725, COL1A1 rs2269336, and MUC15 rs17309195, while MMP14 rs17884816 and MUC15 rs10430847, rs2063278, and rs967490 were associated with increased capsule formation. The MUC15 block 2 haplotype was associated with increased capsule formation. Conclusions: MUC15, MMP14, BRAF, and COL1A1 gene polymorphisms are associated with capsule formation in HCC. Studies involving larger samples are needed to confirm our results.

Outcome-based student assessment enhances academic performance in basic medical laboratory course.

Basic medical laboratory courses (BMLCs) play an important role in medical educational courses helping the student acquire three important skills of surgical operating, collaborative learning, and problem solving. The outcome-based student assessment (OBSA) is a learning evaluation method that establishes specific evaluation points based on performance of students in three aspects: surgical operating, collaborative learning, and problem solving in the BMLC curriculum practices. The purpose of the present randomized controlled trial study is to explore the efficiency of OBSA program in BMLCs. The 233 students attending BMLCs were randomly divided into 2 groups, 118 in the OBSA group and 115 in the control group. We conducted multiple-choice examination questions (MCQs) test and two questionnaires with the method of two-sample t test for statistics. The results of MCQs in total eight BMLC blocks showed that the academic performance of the OBSA group was significantly better than that of the control group (P < 0.05). In addition, the average scores of direct observation of procedural skills (DOPS) and mini-experimental evaluation exercise in OBSA group were significantly higher than those in control group (P < 0.05). The majority of the medical students preferred the OBSA and considered OBSA could effectively improve their surgical operating skills (83.9%), collaborative learning skills (92.1%), and problem-solving skills (91.1%). From the above, OBSA is an effective evaluation method for the implementation of the BMLC curriculum.

Analgesic Effect of Noninvasive Brain Stimulation for Neuropathic Pain Patients: A Systematic Review.

INTRODUCTION: The objective of this review is to systematically summarize the consensus on best practices for different NP conditions of the two most commonly utilized noninvasive brain stimulation (NIBS) technologies, repetitive transcranial magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS). METHODS: PubMed was searched according to the predetermined keywords and criteria. Only English language studies and studies published up to January 31, 2020 were taken into consideration. Meta-analyses, reviews, and systematic reviews were excluded first, and those related to animal studies or involving healthy volunteers were also excluded. Finally, 29 studies covering 826 NP patients were reviewed. RESULTS: The results from the 24 enrolled studies and 736 NP patients indicate that rTMS successfully relieved the pain symptoms of 715 (97.1%) NP patients. Also, five studies involving 95 NP patients (81.4%) also showed that tDCS successfully relieved NP. In the included studied, the M1 region plays a key role in the analgesic treatment of NIBS. The motor evoked potentials (MEPs), the 10-20 electroencephalography system (EEG 10/20 system), and neuro-navigation methods are used in clinical practice to locate therapeutic targets. Based on the results of the review, the stimulation parameters of rTMS that best induce an analgesic effect are a stimulation frequency of 10-20 Hz, a stimulation intensity of 80-120% of RMT, 1000-2000 pulses, and 5-10 sessions, and the most effective parameters of tDCS are a current intensity of 2 mA, a session duration of 20-30 min, and 5-10 sessions. CONCLUSIONS: Our systematically reviewed the evidence for positive and negative responses to rTMS and tDCS for NP patient care and underscores the analgesic efficacy of NIBS in patients with NP. The treatment of NP should allow the design of optimal treatments for individual patients.

The development of a predictive risk model on post-ablation hemobilia: a multicenter matched case-control study.

OBJECTIVE: This study aimed to develop a predictive risk model for post-ablation hemobilia. METHODS: This was a retrospective, multicenter, matched case-control study. The case group comprised patients with hepatocellular carcinoma who developed post-ablation hemobilia (n = 21); the control group (n = 63) comprised patients with hepatocellular carcinoma but no post-ablation hemobilia; for each case, we included three controls matched for age, sex, platelet count, year of ablation therapy, and center. Univariate and multivariate regression analyses were performed to identify the risk factors for hemobilia. A risk score model was developed based on adjusted odds ratios (ORs). RESULTS: The independent risk factors for occurrence of post-ablation hemobilia were maximum tumor diameter >47 mm [OR = 5.983, 95% CI (1.134-31.551)] and minimum distance from the applicator to the portal trunk ≤8 mm [OR = 4.821, 95% CI (1.225-18.975)]. The risk model was developed using the adjusted ORs; thus a score of 6 was assigned to the former and a score of 5 for the latter. The area under the curve of this risk model was 0.76. Significant hemodynamic instability and inaccurate embolization might increase the risk of recurrence of hemobilia. CONCLUSION: Tumor size >47 mm and distance of the applicator from the portal trunk ≤8 mm are independent risk factors for hemobilia. A predictive risk model for post-ablation hemobilia was developed using these risk factors. ADVANCES IN KNOWLEDGE: This is the first study that developed a risk score model of post-ablation hemobilia. Risk factors of the recurrence of post-ablation hemobilia were also been identified.

The HIV prevalence in older men who have sex with men in Western & Central Europe and North America-a meta-analysis.

The age of patients living with human immunodeficiency virus (HIV) is increasing and the greatest proportion of aged HIV patients occurred in Western and Central Europe and North America (WCENA). In aged HIV patients in WCENA, older MSM is the main population. The aim of our study was to evaluate the HIV prevalence in older MSM in WCENA. A meta-analysis was conducted. We searched Medline, Embase, PsycINFO, Web of Science, Cochrane library, Ageline databases, and government websites. Studies that estimated HIV prevalence in older MSM in WCENA were selected. The pooled HIV prevalence and odds ratio (OR) of the risk of living with HIV in older MSM were calculated. In total of 23000 records were initially records were identified and 12 records were included. The total sample size of older MSM was 6118. The pooled HIV prevalence in older MSM in WCENA was 26% (95% CI 18%-33%), which was much higher than that in younger MSM (18%, 95% CI 14%-21%). Notably, the HIV prevalence in older MSM has been continuously increasing in the past two decades in WCENA, raising from 16% to 33%. The pooled OR for older MSM to be living with HIV was 1.68 compared to younger MSM. The HIV prevalence in older MSM in WCENA is disproportionately high, with a continuously increasing trend in the past two decades. Older MSM also carry significantly higher risk of living with HIV than younger MSM.

Association between education level and HIV-associated neurocognitive disorder: a systematic review and meta-analysis.

In the era of antiretroviral treatment, human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) is common in HIV-positive (HIV+) patients, with an incidence of 30-50%. The relationship between education level and HAND has been evaluated in some studies, however, the results were inconsistent. The aim of this meta-analysis was to provide compelling evidence on the association between education level and the risk of HAND. Reports were searched for in the databases of Medline, Embase and PsyclNFO. Studies evaluating the relationship between education level and HAND in adult HIV+ patients were included. The pooled odds ratio/risk ratio was analysed by using the random-effects model. Two subgroup analyses were performed according to the adjustment of educational level in the neurocognitive impairment assessment and the income level. In total, 18 studies were included. Six studies and 12 studies reported education level as the continuous variable and categorical variable, respectively. The methods used for the assessment of neurocognitive impairment in included studies were neuropsychological battery tests (n = 10), HIV Dementia Scale (n = 1), the International HIV Dementia Scale (n = 6) and the Chinese version of the Montreal Cognitive Assessment (n = 1). The result showed that the risk of HAND in HIV+ patients who have lower education attainment was significantly higher than that in HIV+ patients who have higher education attainment. In conclusion, this meta-analysis demonstrated that HIV+ patients who have low education attainment carry higher risk of developing HAND compared with HIV+ patients who have high education attainment. This study highlighted the importance of early neurological screening for HIV+ patients who have low education level.

Percutaneous Radiofrequency Ablation Combined With Transarterial Chemoembolization Plus Sorafenib for Large Hepatocellular Carcinoma Invading the Portal Venous System: A Prospective Randomized Study.

BACKGROUND: Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) portends a worse prognosis. The objective of this study was to compare the efficacy of percutaneous radiofrequency ablation (RFA) combined with transarterial chemoembolization (TACE) plus sorafenib to that of the most commonly utilized regimen of TACE plus sorafenib in large HCCs with type I/II PVTT. METHODS: An open-label, single-center, prospective, randomized trial of participants with tumors ≥5 cm and type I/II PVTT was performed. Participants with previously untreated HCCs were divided into two groups: RFA + cTACE + sorafenib (study group, n = 40) and cTACE + sorafenib (control group, n = 40). The primary endpoint was the objective response rate (ORR), the secondary endpoints included the overall survival (OS); time to progression (TTP); and toxicity. Prognostic factors were analyzed using cox-regression analysis. RESULTS: 80 patients were enrolled into this study with integrated clinical data. Under a median follow-up of 506 days, the median age was 57.5 years (range: 28-80 years). The ORR of study group was higher than control group (70% vs 22.5%, p<0.001). Furthermore, the median OS of study group was superior to that of control group (468 days vs 219 days, HR: 0.44 [95% CI: 0.25-0.78], P = 0.005). Adverse events occurred with 100% probability in both groups (p>0.99), but no treatment-related deaths were recorded. Tumor encapsulation and attaining treatment response predict favorable OS in a multivariate Cox model. The rates of adverse events in both groups were 100% (p>0.99). There were no treatment-related deaths. CONCLUSIONS: RFA combined with TACE plus sorafenib is a safe, well-tolerated three-modality treatment for large HCCs with types I/II PVTT, and it demonstrated better efficacy than TACE plus sorafenib alone.

Safety and efficacy of the combination therapy of transcatheter arterial chemoembolization and ablation for hepatocellular carcinoma with inferior vena cava tumor thrombus: A consecutive case series.

This study was designed to propose a classification of inferior vena cava tumor thrombus (IVCTT) and retrospectively evaluate the safety and efficacy of the combination therapy of transcatheter arterial chemoembolization (TACE) and sequential percutaneous ablation for hepatocellular carcinoma (HCC) with IVCTT. All HCC patients with IVCTT who underwent the combination therapies of TACE and sequential percutaneous ablation therapy between January 2015 and December 2017 in Beijing Youan Hospital were included in the study. The demographic, clinical, and pathological data were recorded. The response rate and overall survival (OS) rate were statistically analyzed. A classification system of IVCTT types was proposed based on the anatomical structure and ablation technique, which contained five types of IVCTT. Different types of IVCTT require different ablation strategies. For the response rate of IVCTT, complete response was achieved in all six patients. The 1- and 2-year OS rates were 88.3% and 55.6%, respectively. The new classification system and corresponding ablation strategies proposed in this study provided guidance for the use of ablation therapy for IVCTT. The combination therapy of TACE and ablation is effective and safe for treating HCC with IVCTT.

Visual Saliency via Embedding Hierarchical Knowledge in a Deep Neural Network.

Deep neural networks (DNNs) have been extensively applied in image processing, including visual saliency map pre-diction of images. A major difficulty in using a DNN for visual saliency prediction is the lack of labeled ground truth of visual saliency. A powerful DNN usually contains a large number of trainable parameters. This condition can easily lead to model over-fitting. In this study, we develop a novel method that over-comes such difficulty by embedding hierarchical knowledge of existing visual saliency models in a DNN. We achieve the objective of exploiting the knowledge contained in the existing visual sali-ency models by using saliency maps generated by local, global, and semantic models to tune and fix about 92.5% of the parame-ters in our network in a hierarchical manner. As a result, the number of trainable parameters that need to be tuned by the ground truth is considerably reduced. This reduction enables us to fully utilize the power of a large DNN and overcome the issue of over-fitting at the same time. Furthermore, we introduce a simple but very effective center prior in designing the learning cost function of the DNN by attaching high importance to the errors around the image center. We also present extensive experimental results on four commonly used public databases to demonstrate the superiority of the proposed method over classical and state-of-the-art methods on various evaluation metrics.

Clinical outcomes of percutaneous thermal ablation for pulmonary metastases from hepatocellular carcinoma: a retrospective study.

Purpose: To determine the effectiveness of ablation for pulmonary metastases (PM) from hepatocellular carcinoma (HCC).Methods: Between 2010 and 2017, the study analyzed 39 patients who had a median age of 59 years. Primary HCC was under control and the number of PM was less than 5 (median: 2), with a maximum diameter of ≤60 mm (median: 15 mm). The primary endpoints were overall survival (OS) and local tumor progression-free survival (LTPFS). Secondary endpoints included technique success (TS), complication and tumor response. TS referred to PM treated using the treatment protocol. Multivariate analysis using the Cox proportional hazard model was conducted on the potential risk factors (univariate: p < 0.5) to determine the independent factors (multivariate: p < 0.05).Results: The TS rate was 100%. Major complications included pneumothorax (n = 3) requiring chest tube placement and pleural effusion requiring drainage (n = 2). Complete ablation was achieved in 32/38 patients (valid percent: 84.2%) at 1 month after ablation. The 1-, 3- and 5-year OS rates were 79.8, 58 and 30.9%, respectively. The 1-, 3- and 5-year LTPFS rates were 60.7, 34.2 and 22.8%, respectively. The extent (unilateral vs. bilateral) of PM (hazard ratio (HR): 0.197, 95% confidence interval (CI): 0.043-0.890, p = 0.035) and the number (≤2 vs. >2) of PM (HR: 0.555, 95% CI: 0.311-0.991, p = 0.047) were found to be the independent risk factors for predicting OS.Conclusion: Percutaneous thermal ablation is a safe and effective treatment for PM from HCC.

Marker controlled superpixel nuclei segmentation and automatic counting on immunohistochemistry staining images.

MOTIVATION: For the diagnosis of cancer, manually counting nuclei on massive histopathological images is tedious and the counting results might vary due to the subjective nature of the operation. RESULTS: This paper presents a new segmentation and counting method for nuclei, which can automatically provide nucleus counting results. This method segments nuclei with detected nuclei seed markers through a modified simple one-pass superpixel segmentation method. Rather than using a single pixel as a seed, we created a superseed for each nucleus to involve more information for improved segmentation results. Nucleus pixels are extracted by a newly proposed fusing method to reduce stain variations and preserve nucleus contour information. By evaluating segmentation results, the proposed method was compared to five existing methods on a dataset with 52 immunohistochemically (IHC) stained images. Our proposed method produced the highest mean F1-score of 0.668. By evaluating the counting results, another dataset with more than 30 000 IHC stained nuclei in 88 images were prepared. The correlation between automatically generated nucleus counting results and manual nucleus counting results was up to R2 = 0.901 (P < 0.001). By evaluating segmentation results of proposed method-based tool, we tested on a 2018 Data Science Bowl (DSB) competition dataset, three users obtained DSB score of 0.331 ± 0.006. AVAILABILITY AND IMPLEMENTATION: The proposed method has been implemented as a plugin tool in ImageJ and the source code can be freely downloaded. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Long-term outcome and prognostic nomogram for intrahepatic cholangiocarcinoma after thermal ablation: a retrospective study.

BACKGROUND: To evaluate the efficacy of thermal ablation and transcatheter arterial chemoembolization (TACE) in treating intrahepatic cholangiocarcinoma (ICC), and to propose a prognostic nomogram to predict overall survival (OS) after ablation. METHODS: ICC patients (n=58) undergoing percutaneous CT-guided ablation with or without pre-ablation TACE at our institute from 2009 to 2013 were enrolled in the primary cohort. All treatments were performed under conscious sedation and local anesthesia. Prognostic factors for OS were identified to establish the nomogram. The nomogram was accessed by the concordance index (C-index) and calibration curve, and compared with 11 currently available prognostic systems. The nomogram was further evaluated in a validation cohort (n=19) of patients with ICC who underwent thermal ablation and TACE from 2014 to 2016. RESULTS: In the primary cohort, the median OS was 17.9 months and the 1-, 3-, 5-year OS rates were 69.6%, 29.5%, 23.6%, respectively. Three single independent predictors (number of tumors, vascular invasion and lymph node metastasis) for OS were identified by multivariate analysis and used to formulate the nomogram. The C-index of the nomogram was 0.834 [95% confidence interval (CI), 0.765 to 0.904], significantly higher than that of ten current prognostic systems for ICC, and similar with that of the Wang nomogram. The performance of the proposed nomogram was also confirmed in the validation cohort (C-index, 0.839). CONCLUSIONS: Thermal ablation appears to be effective for ICC patients. The proposed nomogram is helpful for predicting patient survival after ablation treatment.

Attention by Selection: A Deep Selective Attention Approach to Breast Cancer Classification.

Deep learning approaches are widely applied to histopathological image analysis due to the impressive levels of performance achieved. However, when dealing with high-resolution histopathological images, utilizing the original image as input to the deep learning model is computationally expensive, while resizing the original image to achieve low resolution incurs information loss. Some hard-attention based approaches have emerged to select possible lesion regions from images to avoid processing the original image. However, these hard-attention based approaches usually take a long time to converge with weak guidance, and valueless patches may be trained by the classifier. To overcome this problem, we propose a deep selective attention approach that aims to select valuable regions in the original images for classification. In our approach, a decision network is developed to decide where to crop and whether the cropped patch is necessary for classification. These selected patches are then trained by the classification network, which then provides feedback to the decision network to update its selection policy. With such a co-evolution training strategy, we show that our approach can achieve a fast convergence rate and high classification accuracy. Our approach is evaluated on a public breast cancer histopathological image database, where it demonstrates superior performance compared to state-of-the-art deep learning approaches, achieving approximately 98% classification accuracy while only taking 50% of the training time of the previous hard-attention approach.