Fast Filter Pruning via Coarse-to-Fine Neural Architecture Search and Contrastive Knowledge Transfer.

Filter pruning is the most representative technique for lightweighting convolutional neural networks (CNNs). In general, filter pruning consists of the pruning and fine-tuning phases, and both still require a considerable computational cost. So, to increase the usability of CNNs, filter pruning itself needs to be lightweighted. For this purpose, we propose a coarse-to-fine neural architecture search (NAS) algorithm and a fine-tuning structure based on contrastive knowledge transfer (CKT). First, candidates of subnetworks are coarsely searched by a filter importance scoring (FIS) technique, and then the best subnetwork is obtained by a fine search based on NAS-based pruning. The proposed pruning algorithm does not require a supernet and adopts a computationally efficient search process, so it can create a pruned network with higher performance at a lower cost than the existing NAS-based search algorithms. Next, a memory bank is configured to store the information of interim subnetworks, i.e., by-products of the above-mentioned subnetwork search phase. Finally, the fine-tuning phase delivers the information of the memory bank through a CKT algorithm. Thanks to the proposed fine-tuning algorithm, the pruned network accomplishes high performance and fast convergence speed because it can take clear guidance from the memory bank. Experiments on various datasets and models prove that the proposed method has a significant speed efficiency with reasonable performance leakage over the state-of-the-art (SOTA) models. For example, the proposed method pruned the ResNet-50 trained on Imagenet-2012 up to 40.01% with no accuracy loss. Also, since the computational cost amounts to only 210 GPU hours, the proposed method is computationally more efficient than SOTA techniques. The source code is publicly available at https://github.com/sseung0703/FFP.

Validity of fatty liver prediction scores for diagnosis of fatty liver by Fibroscan.

BACKGROUND: The Korea National Health and Nutrition Examination Survey nonalcoholic fatty liver disease (K-NAFLD) score was recently developed with the intent to operationally define nonalcoholic fatty liver disease (NAFLD). However, there remained an external validation that confirmed its diagnostic performance, especially in patients with alcohol consumption or hepatitis virus infection. METHODS: Diagnostic accuracy of the K-NAFLD score was evaluated in a hospital-based cohort consisting of 1388 participants who received Fibroscan®. Multivariate-adjusted logistic regression models and the contrast estimation of receiver operating characteristic curves were used for validation of the K-NAFLD score, fatty liver index (FLI), and hepatic steatosis index (HSI). RESULTS: K-NAFLD-moderate [adjusted odds ratio (aOR) = 2.53, 95% confidence interval (CI): 1.13-5.65] and K-NAFLD-high (aOR = 4.14, 95% CI: 1.69-10.13) groups showed higher risks of fatty liver compared to the K-NAFLD-low group after adjustments for demographic and clinical characteristics, and FLI-moderate and FLI-high groups revealed aORs of 2.05 (95% CI: 1.22-3.43) and 1.51 (95% CI: 0.78-2.90), respectively. In addition, the HSI was less predictive for Fibroscan®-defined fatty liver. Both K-NAFLD and FLI also demonstrated high accuracy in the prediction of fatty liver in patients with alcohol consumption and chronic hepatitis virus infection, and the adjusted area under curve values were comparable between K-NAFLD and FLI. CONCLUSIONS: Externally validation of the K-NAFLD and FLI showed that these scores may be a useful, noninvasive, and non-imaging modality for the identification of fatty liver. In addition, these scores also predicted fatty liver in patients with alcohol consumption and chronic hepatitis virus infection.

A Multi-Center, Double-Blind Randomized Controlled Phase III Clinical Trial to Evaluate the Antiviral Activity and Safety of DA-2802 (Tenofovir Disoproxil Orotate) and Viread (Tenofovir Disoproxil Fumarate) in Chronic Hepatitis B Patients.

BACKGROUND: Tenofovir disoproxil fumarate (TDF, Viread®) had been used as a standard treatment option of chronic hepatitis B (CHB). This clinical trial was conducted to evaluate the efficacy and safety of DA-2802 (tenofovir disoproxil orotate) compared to TDF. METHODS: The present study was a double blind randomized controlled trial. Patients with CHB were recruited from 25 hospitals in Korea and given DA-2802 at a dose of 319 mg once daily or Viread® at a dose of 300 mg once daily for 48 weeks from March 2017 to January 2019. Change in hepatitis B virus (HBV) DNA level at week 48 after dosing compared to baseline was the primary efficacy endpoint. Secondary efficacy endpoints were proportions of subjects with undetectable HBV DNA, those with normal alanine aminotransferase (ALT) levels, and those with loss of hepatitis B envelop antigen (HBeAg), those with loss of hepatitis B surface antigen (HBsAg). Adverse events (AEs) were also investigated. RESULTS: A total of 122 patients (DA-2802 group: n = 61, Viread® group: n = 61) were used as full analysis set for efficacy analysis. Mean age, proportion of males, laboratory results and virologic characteristics were not different between the two groups. The change in HBV DNA level at week 48 from baseline was -5.13 ± 1.40 in the DA-2802 group and -4.97 ± 1.40 log10 copies/mL in the Viread® group. The analysis of primary endpoint using the nonparametric analysis of covariance showed statistically significant results (P < 0.001), which confirmed non-inferiority of DA-2802 to Viread® by a prespecified noninferiority margin of 1. The proportion of undetectable HBV DNA was 78.7% in the DA-2802 group and 75.4% in the Viread® group (P = 0.698). The proportion of subjects who had normal ALT levels was 75.4% in the DA-2802 group and 73.3% in the Viread® group (P = 0.795). The proportion of those with HBeAg loss was 8.1% in the DA-2802 group and 10.8% in the Viread® group (P = 1.000). No subject showed HBsAg loss. The frequency of AEs during treatment was similar between the two groups. Most AEs were mild to moderate in severity. CONCLUSION: DA-2802 is considered an effective and safe treatment for patients with CHB. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02967939.

Knowledge Transfer via Decomposing Essential Information in Convolutional Neural Networks.

Knowledge distillation (KD) from a "teacher" neural network and transfer of the knowledge to a small student network is done to improve the performance of the student network. This method is one of the most popular techniques to lighten convolutional neural networks (CNNs). Many KD algorithms have been proposed recently, but they still cannot properly distill essential knowledge of the teacher network, and the transfer tends to depend on the spatial shape of the teacher's feature map. To solve these problems, we propose a method to transfer knowledge independently of the spatial shape of the teacher's feature map, which is major information obtained by decomposing the feature map through singular value decomposition (SVD). In addition, we present a multitask learning method that enables the student to learn the teacher's knowledge effectively by adaptively adjusting the teacher's constraints to the student's learning speed. Experimental results show that the proposed method performs 2.37% better on the CIFAR100 data set and 2.89% better on the TinyImageNet data set than the state-of-the-art method. The source code is publicly available at https://github.com/sseung0703/KD_methods_with_TF.

Visual Scene-Aware Hybrid and Multi-Modal Feature Aggregation for Facial Expression Recognition.

Facial expression recognition (FER) technology has made considerable progress with the rapid development of deep learning. However, conventional FER techniques are mainly designed and trained for videos that are artificially acquired in a limited environment, so they may not operate robustly on videos acquired in a wild environment suffering from varying illuminations and head poses. In order to solve this problem and improve the ultimate performance of FER, this paper proposes a new architecture that extends a state-of-the-art FER scheme and a multi-modal neural network that can effectively fuse image and landmark information. To this end, we propose three methods. To maximize the performance of the recurrent neural network (RNN) in the previous scheme, we first propose a frame substitution module that replaces the latent features of less important frames with those of important frames based on inter-frame correlation. Second, we propose a method for extracting facial landmark features based on the correlation between frames. Third, we propose a new multi-modal fusion method that effectively fuses video and facial landmark information at the feature level. By applying attention based on the characteristics of each modality to the features of the modality, novel fusion is achieved. Experimental results show that the proposed method provides remarkable performance, with 51.4% accuracy for the wild AFEW dataset, 98.5% accuracy for the CK+ dataset and 81.9% accuracy for the MMI dataset, outperforming the state-of-the-art networks.

Aspartate Aminotransferase-to-Platelet Ratio or Fibros-4 Index Predicts the Development of Hepatocellular Carcinoma in Chronic Hepatitis C Patients with Sustained Virologic Response to Interferon Therapy.

The risk of hepatocellular carcinoma (HCC) is not completely eliminated in chronic hepatitis C (CHC) patients even after viral eradication. There are few studies in predicting the development of HCC using biomarker in CHC patients with sustained virologic response (SVR). We evaluated the role of the aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) in predicting HCC development in 295 patients with SVR after interferon therapy. The annual incidence of HCC was 0.55% (95% confidence interval: 0.31-0.96). It was higher in patients with a pretreatment APRI ≥2.0 than in those with an APRI <2.0 (1.82% versus 0.17%; P = 0.0001) and in patients with a FIB-4 ≥ 3.25 compared with those with a FIB-4 < 3.25. (1.50% versus 0.07%; P = 0.0001). The annual incidence of HCC was higher in patients with a post-treatment APRI ≥0.5 than in those with an APRI <0.5 (1.67% versus 0.07%; P < 0.0001) and in patients with a post-treatment FIB-4 ≥ 2.5 compared with those with a FIB-4 < 2.5 (1.49% versus 0.01%; P = 0.0003). Among pretreatment variables, male gender, albumin, APRI, or FIB-4 were independent predictors for HCC. Among post-treatment variables, APRI or FIB-4 was an independent predictor for HCC. HCC surveillance should be performed in these high-risk patients.

Development and surveillance of hepatocellular carcinoma in patients with sustained virologic response after antiviral therapy for chronic hepatitis C.

Hepatitis C virus (HCV) infection is a major risk factor for liver cirrhosis and hepatocellular carcinoma (HCC), and is a leading cause of liver-related deaths worldwide. Recently available direct-acting antiviral agent is very safe and highly effective (>95% sustained virologic response, SVR) against all genotypes of HCV. Achievement of SVR has been associated with a significant reduction of hepatic decompensation, development of HCC, and liver-related mortality. However, HCC risk is not eliminated even after SVR. The annual incidences of HCC in advanced fibrosis or cirrhosis have been estimated to be up to 2.5-4.5% even in patients with SVR. Therefore, surveillance for HCC is recommended in this high-risk patients. In this review, we will describe the clinical outcomes and the risk of HCC in patients with SVR and suggest who should receive surveillance for HCC.

Chronic Hepatitis B Infection Is Significantly Associated with Chronic Kidney Disease: a Population-based, Matched Case-control Study.

BACKGROUND: Hepatitis B virus (HBV) infection leads to hepatic and extrahepatic manifestations including chronic kidney disease (CKD). However, the association between HBV and CKD is not clear. This study investigated the association between chronic HBV infection and CKD in a nationwide multicenter study. METHODS: A total of 265,086 subjects who underwent health-check examinations in 33 hospitals from January 2015 to December 2015 were enrolled. HBV surface antigen (HBsAg) positive cases (n = 10,048), and age- and gender-matched HBsAg negative controls (n = 40,192) were identified. CKD was defined as a glomerular filtration rate (GFR) < 60 mL/min/1.73 m2 or proteinuria as at least grade 2+ of urine protein. RESULTS: HBsAg positive cases showed a significantly higher prevalence of GFR < 60 mL/min/1.73 m2 (3.3%), and proteinuria (18.9%) than that of the controls (2.6%, P < 0.001, and 14.1%, P < 0.001, respectively). In the multivariate analysis, HBsAg positivity was an independent factor associated with GFR < 60 mL/min/1.73 m2 along with age, blood levels of albumin, bilirubin, anemia, and hemoglobin A1c (HbA1c). Likewise, HBsAg positivity was an independent factor for proteinuria along with age, male, blood levels of bilirubin, protein, albumin, and HbA1c. A subgroup analysis showed that HBsAg positive men but not women had a significantly increased risk for GFR < 60 mL/min/1.73 m2. CONCLUSION: Chronic HBV infection was significantly associated with a GFR < 60 mL/min/1.73 m2 and proteinuria (≥ 2+). Therefore, clinical concern about CKD in chronic HBV infected patients, especially in male, is warranted.

Endoscopic Ultrasound-Guided Perirectal Abscess Drainage without Drainage Catheter: A Case Series.

A perirectal abscess is a relatively common disease entity that occurs as a postsurgical complication or as a result of various medical conditions. Endoscopic ultrasound (EUS)-guided drainage was recently described as a promising alternative treatment. Previous reports have recommended placement of a drainage catheter through the anus for irrigation, which is inconvenient to the patient and carries a risk of accidental dislodgement. We report four cases of perirectal abscess that were successfully treated with only one or two 7 F double pigtail plastic stent placements and without a drainage catheter for irrigation.

Regression of esophageal varices and splenomegaly in two patients with hepatitis-C-related liver cirrhosis after interferon and ribavirin combination therapy.

Some recent studies have found regression of liver cirrhosis after antiviral therapy in patients with hepatitis C virus (HCV)-related liver cirrhosis, but there have been no reports of complete regression of esophageal varices after interferon/peg-interferon and ribavirin combination therapy. We describe two cases of complete regression of esophageal varices and splenomegaly after interferon-alpha and ribavirin combination therapy in patients with HCV-related liver cirrhosis. Esophageal varices and splenomegaly regressed after 3 and 8 years of sustained virologic responses in cases 1 and 2, respectively. To our knowledge, this is the first study demonstrating that complications of liver cirrhosis, such as esophageal varices and splenomegaly, can regress after antiviral therapy in patients with HCV-related liver cirrhosis.

Regression of esophageal varices during entecavir treatment in patients with hepatitis-B-virus-related liver cirrhosis.

Recent studies suggest that liver cirrhosis is reversible after administering oral nucleos(t)ide analogue therapy to patients with hepatitis B virus (HBV) infection. However, few studies have addressed whether esophageal varices can regress after such therapy. We report a case of complete regression of esophageal varices during entecavir therapy in patients with HBV-related liver cirrhosis, suggesting that complications of liver cirrhosis such as esophageal varices can regress after the long-term suppression of HBV replication.

Erratum.

[This corrects the article on p. 355 in vol. 20, PMID: 25548741.][This corrects the article on p. 368 in vol. 20, PMID: 25548743.].

Influence of the basal core promoter and precore mutation on replication of hepatitis B virus and antiviral susceptibility of different genotypes.

Mutations in the basal core promoter (BCP) and precore (PC) regions of the hepatitis B virus (HBV) are more common in genotypes B and C than in genotype A, suggesting that these mutations might affect replication competency depending on genotype. The purpose of the study was to investigate the influence of these mutations on the capacity of HBV for replication and antiviral drug susceptibility according to genotype. Genotypes A, B, and C of HBV strains with a BCP mutation, PC mutation, or BCP + PC mutation were made by site-directed mutagenesis. Replication competency of each construct and susceptibility to nucleos(t) ide analogues were tested in an Huh7 cell line. In genotype A, the BCP and BCP + PC mutations increased the viral replication around 6.5 times compared with the wild type, and the PC mutation alone similarly increased the viral replication around three times. In genotypes B and C, all three mutant types increased viral replication to a similar extent, regardless of mutation pattern. Interestingly, the BCP mutation appeared to have a greater effect on viral replication in genotype A than in genotypes B and C. This finding was unexpected because the BCP mutation is more common in HBV genotypes B and C. Moreover, the BCP, PC, and BCP + PC mutations decreased the sensitivity of HBV to antiviral agents to various degrees (2- to 10-fold) regardless of genotype. In conclusion, BCP and PC mutations increased viral replication regardless of HBV genotype and decreased in vitro antiviral susceptibility to the nucleos(t) ide analogues.

Is it necessary to delay antiviral therapy for 3-6 months to anticipate HBeAg seroconversion in patients with HBeAg-positive chronic hepatitis B in endemic areas of HBV genotype C?

BACKGROUND/AIMS: Spontaneous HBeAg seroconversion occurs frequently in the immune reactive phase in HBeAg-positive chronic hepatitis B (CHB). Therefore, observation for 3-6 months before commencing antiviral therapy is recommended in patients with alanine aminotransferase (ALT) levels that exceed twice the upper limit of normal (ULN). However, HBeAg seroconversion occurs infrequently in patients infected with hepatitis B virus (HBV) genotype C. The aim of the present study was to determine whether the waiting policy is necessary in endemic areas of HBV genotype C infection. METHODS: Ninety patients with HBeAg-positive CHB were followed prospectively without administering antiviral therapy for 6 months. Antiviral therapy was initiated promptly at any time if there was any evidence of biochemical (i.e., acute exacerbation of HBV infection or aggravation of jaundice) or symptomatic deterioration. After 6 months of observation, antiviral therapy was initiated according to the patient's ALT and HBV DNA levels. RESULTS: Only one patient (1.1%) achieved spontaneous HBeAg seroconversion. Biochemical and symptomatic deterioration occurred before 6 months in 17 patients (18.9%) and 5 patients, respectively. High ALT and HBV DNA levels were both independent risk factors for biochemical deterioration. Of 15 patients with HBV DNA ≥ 5.1 × 10(7) IU/mL and ALT ≥ 5 × ULN, biochemical deterioration occurred in 7 (46.7%), including 1 patient receiving liver transplantation due to liver failure. CONCLUSIONS: Spontaneous HBeAg seroconversion in patients with HBeAg-positive CHB is rare within 6 months. Biochemical deterioration was common and may lead to liver failure. Immediate antiviral therapy should be considered, especially in patients with high ALT and HBV DNA levels in endemic areas of genotype C infection.

Predictors of spontaneous viral clearance and outcomes of acute hepatitis C infection.

BACKGROUND/AIMS: This study evaluated the predictors of spontaneous viral clearance (SVC), as defined by two consecutive undetectable hepatitis C virus (HCV) RNA tests performed ≥ 12 weeks apart, and the outcomes of acute hepatitis C (AHC) demonstrating SVC or treatment-induced viral clearance. METHODS: Thirty-two patients with AHC were followed for 12-16 weeks without administering antiviral therapy. RESULTS: HCV RNA was undetectable at least once in 14 of the 32 patients. SVC occurred in 12 patients (37.5%), among whom relapse occurred in 4. SVC was exhibited in 8 of the 11 patients exhibiting undetectable HCV RNA within 12 weeks. HCV RNA reappeared in three patients (including two patients with SVC) exhibiting undetectable HCV RNA after 12 weeks. SVC was more frequent in patients with low viremia than in those with high viremia (55.6% vs. 14.3%; P=0.02), and in patients with HCV genotype non-1b than in those with HCV genotype 1b (57.1% vs. 22.2%; P=0.04). SVC was more common in patients with a ≥ 2 log reduction of HCV RNA at 4 weeks than in those with a smaller reduction (90% vs. 9.1%, P<0.001). A sustained viral response was achieved in all patients (n=18) receiving antiviral therapy. CONCLUSIONS: Baseline levels of HCV RNA and genotype non-1b were independent predictors for SVC. A ≥ 2 log reduction of HCV RNA at 4 weeks was a follow-up predictor for SVC. Undetectable HCV RNA occurring after 12 weeks was not sustained. All patients receiving antiviral therapy achieved a sustained viral response. Antiviral therapy should be initiated in patients with detectable HCV RNA at 12 weeks after the diagnosis.

Different mechanism of selection of adefovir-resistant mutant viruses during adefovir monotherapy in patients with lamivudine-resistant chronic hepatitis B.

BACKGROUND: Adefovir (ADV) resistance is more frequent in lamivudine (LMV)-resistant chronic hepatitis B (CHB) patients than in nucleos(t)ide analogue-naïve patients. The majority of LMV-resistant mutants harbor the rtM204V/I mutation, while a minor fraction harbor the rtA181V/T mutation. We aimed to elucidate the mechanism of the high rate of ADV resistance in LMV-resistant patients during ADV therapy. METHODS: We performed a clonal analysis of HBV reverse transcriptase in treatment-naïve (n = 3) and LMV-resistant patients before ADV therapy (n = 14). Dynamic changes in the viral population (n = 9) during ADV therapy were also analyzed. RESULTS: Before ADV therapy, rtA181V/T was observed in 30 of 680 clones (4.4%) from 7 patients with LMV resistance under dominant rt204V/I mutation and in one of 150 clones in treatment-naïve patients. The rtA181V/T mutation was more frequently found in clones from LMV-resistant patients than in treatment-naïve patients (p = 0.029). The rtN236T mutation was not observed in any clone. During ADV therapy, most rtM204V/I mutants were replaced by wild type in all 3 patients without the rtA181V/T mutation and in one patient with the rtA181V/T mutation. Subsequently, wild type was replaced by the rtN236T and/or rtA181V/T mutant. In patients with the rtA181V/T mutation (n = 6), the rtA181V/T mutant overtook the rtM204V/I mutant in 3 of 4 patients with ADV resistance. In 2 patients without ADV resistance, most of the viral population was replaced by wild type by the last follow-up. CONCLUSION: The high rate of ADV resistance in patients with LMV-resistance might be attributable to preexisting rtA181V/T mutant virus.

Power-constrained contrast enhancement algorithm using multiscale retinex for OLED display.

This paper presents a power-constrained contrast enhancement algorithm for organic light-emitting diode display based on multiscale retinex (MSR). In general, MSR, which is the key component of the proposed algorithm, consists of power controllable log operation and subbandwise gain control. First, we decompose an input image to MSRs of different sub-bands, and compute a proper gain for each MSR. Second, we apply a coarse-to-fine power control mechanism, which recomputes the MSRs and gains. This step iterates until the target power saving is accurately accomplished. With video sequences, the contrast levels of adjacent images are determined consistently using temporal coherence in order to avoid flickering artifacts. Finally, we present several optimization skills for real-time processing. Experimental results show that the proposed algorithm provides better visual quality than previous methods, and a consistent power-saving ratio without flickering artifacts, even for video sequences.

[A case of acute pancreatitis and acute hepatitis caused by ingestion of Ceramium kondoi].

In Korea, the use of herbal remedies is a common cause of drug-induced liver injury. However, the occurrence of both acute pancreatitis and acute hepatitis after taking herbal remedies has rarely been reported. Herein, we report a case of concurrent acute pancreatitis and acute hepatitis associated with Ceramium kondoi ingestion. A 58-year-old woman was diagnosed with advanced gastric cancer 7 months ago. Total gastrectomy and adjuvant chemotherapy was performed without complications. The patient had been well until recently, when she presented with severe abdominal pain after ingestion of Ceramium kondoifor 4 weeks. The laboratory findings demonstrated elevated liver enzymes and lipase, and abdominal computed tomography revealed pancreas swelling with fat infiltration. The diagnosis was made based on the diagnostic criteria for drug induced pancreatitis and the Russel Uclaf Causality Assessment Method scale for drug-induced liver injury. After cessation of Ceramium kondoi, she showed clinical and biochemical improvement.

[Clarithromycin-resistant Helicobacter pylori associated with 23S rRNA point mutations in Jeju Island].

BACKGROUND/AIMS: The point mutations in 23S rRNA gene accounts for the majority of the clarithromycin resistance of Helicobacter pylori. This study aimed to investigate the association between the clarithromycin-resistance of H. pylori and the failure of primary H. pylori eradication therapy in Jeju Island. METHODS: Between April 2011 and October 2012, 6,937 patients underwent endoscopy, and H. pylori infection was evaluated in 2,287 patients (33.0%). Total of 110 patients with H. pylori infection were treated with proton pump inhibitor (PPI)-based triple therapy. The result of eradication was evaluated with urea breath test, histology and PCR which were conducted 4 weeks from the last dose of medicine. RESULTS: The patients who had point mutations were 33 (26.0%). A2142G and A2143G mutations were observed in 10 patients (7.9%) and 23 patients (18.1%). Among 110 patients treated with PPI-based triple therapy, the success rate of the eradication therapy was 52.7% (58/110) and 70.7% (58/82) by intention-to-treat and per-protocol analysis, respectively. Fifteen of the 24 patients who failed the eradication therapy showed point mutations; 1 patient (4.2%) showed A2142G mutation and 14 patients (58.3%) showed A2143G mutation. Patients with A2143G mutation H. pylori showed higher failure rate of 87.5%. Patients with A2142G mutation H. pylori showed similar failure rate compared to those of the patients with wild type H. pylori. CONCLUSIONS: In Jeju Island, the frequency of 23S rRNA point mutations is similar (26.0%) with other regions of Korea (15.8-31.3%). A2143G mutation is associated with the failure of H. pylori eradication.