Active Generative Adversarial Network for Image Classification

Sufficient supervised information is crucial for any machine learning models to boost performance. However, labeling data is expensive and sometimes difficult to obtain. Active learning is an approach to acquire annotations for data from a human oracle by selecting informative samples with a high probability to enhance performance. In recent emerging studies, a generative adversarial network (GAN) has been integrated with active learning to generate good candidates to be presented to the oracle. In this paper, we propose a novel model that is able to obtain labels for data in a cheaper manner without the need to query an oracle. In the model, a novel reward for each sample is devised to measure the degree of uncertainty, which is obtained from a classifier trained with existing labeled data. This reward is used to guide a conditional GAN to generate informative samples with a higher probability for a certain label. With extensive evaluations, we have confirmed the effectiveness of the model, showing that the generated samples are capable of improving the classification performance in popular image classification tasks.Comment: AAAI201

Surgical Outcome of Patients Undergoing Pancreaticoduodenectomy: Analysis of a 17-Year Experience at a Single Center

The operative mortality and morbidity of pancreaticoduodenectomy (PD) remain high. We analyzed PD patientsʼ clinical characteristics and surgical outcomes and discuss how PD clinical outcomes could be improved. We retrospectively reviewed the cases of 400 patients who underwent a PD between January 1998 and April 2014 at Okayama University Hospital, a very-high-volume center. We identified and compared the clinical outcomes between two time periods (period 1: 1998-2006 vs. period 2: 2007-2014). The total postoperative mortality and major complication rates were 0.75 and 15.8 , respectively, and the median postoperative length of stay (LOS) was 32 days. Subsequently, patients who underwent a PD during period 2 had a significantly shorter LOS than those who underwent a PD during period 1 (29 days vs. 38.5 days, p＜0.001). The incidence of mortality and major complications did not differ between the two periods. In our multivariate analysis, period 1 was an independent factor associated with a long LOS (p＜0.001). The improvement of the surgical procedure and perioperative care might be related to the shorter LOS in period 2 and ot the consistently maintained low mortality rate after PD. The development of multimodal strategies to accelerate postoperative recovery may further improve PDʼs clinical outcomes

Syndrome of Inappropriate Antidiuretic Hormone Secretion Following Liver Transplantation

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is an extremely rare cause of hyponatremia post-liver transplantation. A 15-year-old Japanese girl with recurrent cholangitis after Kasai surgery for biliary atresia underwent successful living donor liver transplantation. Peritonitis due to gastrointestinal perforation occurred. Hyponatremia gradually developed but improved after hypertonic sodium treatment. One month later, severe hyponatremia rapidly recurred. We considered the hyponatremia’s cause as SIADH. We suspected that tacrolimus was the disease’s cause, so we used cyclosporine instead, plus hypertonic sodium plus water intake restriction, which improved the hyponatremia. Symptomatic hyponatremia manifested by SIADH is a rare, serious complication post-liver transplantation

Novel Urinary Glycan Biomarkers Predict Cardiovascular Events in Patients With Type 2 Diabetes: A Multicenter Prospective Study With 5-Year Follow Up (U-CARE Study 2)

Background: Although various biomarkers predict cardiovascular event (CVE) in patients with diabetes, the relationship of urinary glycan profile with CVE in patients with diabetes remains unclear. Methods: Among 680 patients with type 2 diabetes, we examined the baseline urinary glycan signals binding to 45 lectins with different specificities. Primary outcome was defined as CVE including cardiovascular disease, stroke, and peripheral arterial disease. Results: During approximately a 5-year follow-up period, 62 patients reached the endpoint. Cox proportional hazards analysis revealed that urinary glycan signals binding to two lectins were significantly associated with the outcome after adjustment for known indicators of CVE and for false discovery rate, as well as increased model fitness. Hazard ratios for these lectins (+1 SD for the glycan index) were UDA (recognizing glycan: mixture of Man5 to Man9): 1.78 (95% CI: 1.24-2.55, P = 0.002) and Calsepa [High-Man (Man2-6)]: 1.56 (1.19-2.04, P = 0.001). Common glycan binding to these lectins was high-mannose type of N-glycans. Moreover, adding glycan index for UDA to a model including known confounders improved the outcome prediction [Difference of Harrel's C-index: 0.028 (95% CI: 0.001-0.055, P = 0.044), net reclassification improvement at 5-year risk increased by 0.368 (0.045-0.692, P = 0.026), and the Akaike information criterion and Bayesian information criterion decreased from 725.7 to 716.5, and 761.8 to 757.2, respectively]. Conclusion: The urinary excretion of high-mannose glycan may be a valuable biomarker for improving prediction of CVE in patients with type 2 diabetes, and provides the rationale to explore the mechanism underlying abnormal N-glycosylation occurring in patients with diabetes at higher risk of CVE

Plasma angiotensin-converting enzyme 2 (ACE2) is a marker for renal outcome of diabetic kidney disease (DKD) (U-CARE study 3)

Introduction ACE cleaves angiotensin I (Ang I) to angiotensin II (Ang II) inducing vasoconstriction via Ang II type 1 (AT1) receptor, while ACE2 cleaves Ang II to Ang (1-7) causing vasodilatation by acting on the Mas receptor. In diabetic kidney disease (DKD), it is still unclear whether plasma or urine ACE2 levels predict renal outcomes or not. Research design and methods Among 777 participants with diabetes enrolled in the Urinary biomarker for Continuous And Rapid progression of diabetic nEphropathy study, the 296 patients followed up for 9 years were investigated. Plasma and urinary ACE2 levels were measured by the ELISA. The primary end point was a composite of a decrease of estimated glomerular filtration rate (eGFR) by at least 30% from baseline or initiation of hemodialysis or peritoneal dialysis. The secondary end points were a 30% increase or a 30% decrease in albumin-to-creatinine ratio from baseline to 1 year. Results The cumulative incidence of the renal composite outcome was significantly higher in group 1 with lowest tertile of plasma ACE2 (p=0.040). Group 2 with middle and highest tertile was associated with better renal outcomes in the crude Cox regression model adjusted by age and sex (HR 0.56, 95% CI 0.31 to 0.99, p=0.047). Plasma ACE2 levels demonstrated a significant association with 30% decrease in ACR (OR 1.46, 95% CI 1.044 to 2.035, p=0.027) after adjusting for age, sex, systolic blood pressure, hemoglobin A1c, and eGFR. Conclusions Higher baseline plasma ACE2 levels in DKD were protective for development and progression of albuminuria and associated with fewer renal end points, suggesting plasma ACE2 may be used as a prognosis marker of DKD.Trial registration number UMIN000011525

Fast-track Surgery Protocol for Hepatectomy and the Rate of Surgical Site Infections: A Single-center Study

The fast-track surgery protocol, including perioperative immunonutritional management, is increasingly gaining attention for the prevention of surgical site infections （SSIs）. To analyze the association between the fast-track surgery protocol employed at a single center and outcomes, including SSIs and the length of hospital stays. This retrospective analysis included 217 patients who underwent hepatectomy at the study department between January 2009 and February 2014. Patients were divided into two groups: those managed by a conventional protocol （group C, n＝75） and those managed by the fast-track surgery protocol （group F, n＝142）. There were no significant differences in patient characteristics or factors between the two groups. However, serum albumin and total cholesterol levels before surgery were significantly higher in group F than in group C, and pre-hepatectomy C-reactive protein （CRP） levels were lower in group F than in group C. Moreover, serum albumin and CRP levels at postoperative day 7 were better in group F than in group C. The operations were longer in group F than in group C （312 vs. 286 min） and blood loss volume was less （385 g in group F vs. 428 g in group C）. SSI rates were significantly lower in group F （4.2％, n＝6） than in group C （13.3％, n＝10）, and the length of hospital stay was significantly shorter in group F （16.7 days） than in group C （25.8 days）. The fast-track surgery protocol as a perioperative management strategy may improve preoperative nutritional status and postoperative inflammation, with subsequent reductions in SSI rates and the length of hospital stay in patients undergoing hepatectomy

Feasibility of Precoagulation Without the Pringle Maneuver for Endoscopic Hepatectomy of Cirrhotic Liver

Various methods, devices, and techniques have been developed to improve safety during laparoscopic hepatectomy procedures. Among these, the Pringle maneuver （PM） is widely used to minimize blood loss during liver transections; however, the risk of ischemic injury associated with this technique is increased by poor hepatic reserve and regeneration dysfunction secondary to liver cirrhosis. This retrospective study evaluated the short-term outcomes and feasibility of precoagulation for endoscopic hepatectomy without PM in patients with liver cirrhosis. Eleven patients with liver cirrhosis who also underwent endoscopic hepatectomy for hepatocellular carcinoma were recruited to undergo either microwave tissue coagulation or radiofrequency ablation for precoagulation before liver transection. A wedge resection without the PM was performed in all patients, with seven patients selected for bipolar radiofrequency ablation and four patients for microwave coagulation therapy. The procedures included video-assisted thoracoscopic hepatectomy in two patients and laparoscopic hepatectomy in nine patients. One patient who underwent radiofrequency ablation developed postoperative bleeding （Clavien-Dindo grade Ⅲ）. In conclusion, precoagulation can help to minimize intraoperative blood loss without the PM, contributing to effective resection of liver tumors. We propose that precoagulation could serve as a standard technique for endoscopic hepatectomy in patients with cirrhosis

Cationized liposomal keto-mycolic acids isolated from Mycobacterium bovis bacillus Calmette-Guérin induce antitumor immunity in a syngeneic murine bladder cancer model

Intravesical therapy using Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the most established cancer immunotherapy for bladder cancer. However, its underlying mechanisms are unknown. Mycolic acid (MA), the most abundant lipid of the BCG cell wall, is suspected to be one of the essential active components of this immunogenicity. Here, we developed cationic liposomes incorporating three subclasses (α, keto, and methoxy) of MA purified separately from BCG, using the dendron-bearing lipid D22. The cationic liposomes using D22 were efficiently taken up by the murine bladder cancer cell line MB49 in vitro, but the non-cationic liposomes were not. Lip-kMA, a cationic liposome containing keto-MA, presented strong antitumor activity in two murine syngeneic graft models using the murine bladder cancer cell lines MB49 and MBT-2 in comparison to both Lip-aMA and Lip-mMA, which contained α-MA and methoxy-MA, respectively. Interestingly, Lip-kMA(D12), which was made of D12 instead of D22, did not exhibit antitumor activity in the murine syngeneic graft model using MB49 cells, although it was successfully taken up by MB49 cells in vitro. Histologically, compared to the number of infiltrating CD4 lymphocytes, the number of CD8 lymphocytes was higher in the tumors treated with Lip-kMA. Antitumor effects of Lip-kMA were not observed in nude mice, whereas weak but significant effects were observed in beige mice with natural killer activity deficiency. Thus, a cationized liposome containing keto-MA derived from BCG induced in vivo antitumor immunity. These findings will provide new insights into lipid immunogenicity and the underlying mechanisms of BCG immunotherapy