Sequential Treatment of Biliary Atresia With Kasai Hepatoportoenterostomy and Liver Transplantation: Benefits, Risks, and Outcome in 393 Children

Introduction: Surgical treatment of biliary atresia (BA) is still based on sequential strategy with Kasai hepatoportoenterostomy (KP) followed by liver transplantation (LT), in case of complicated secondary biliary cirrhosis. Concerns have been expressed regarding the risks of LT related to previous KP, suggesting primary LT as an exclusive treatment of BA.Methods: Single-center retrospective analysis including 393 pediatric patients who underwent LT for BA from 1993 to 2018, categorized into two groups: with (KP) or without (NoKP) previous KP. Pre-LT clinical condition was estimated considering age at LT, time on waiting list, pediatric end-stage liver disease score (PELD), and presence of portal vein hypoplasia. Post-LT outcome was evaluated considering patient and graft survival rates, and need for early reoperation due to abdominal or graft-related complications (<45 days after LT).Results: Two-hundred ninety-six patients (75.3%) were categorized in the KP group, and 97 (24.7%) in the NoKP group. Median age at LT was 1.14 years in the KP group and 0.85 years in the NoKP group (p < 0.0001). PELD score was significantly less severe in KP patients (p < 0.05). One-year patient survival rates were 96.9 and 96.8% in the KP and NoKP groups, respectively (p = 0.43), and the corresponding graft survival was 92.5 and 94.8% (p = 0.97). The need for early reoperation was more frequent in the KP group (29.8%) vs. NoKP group (12.4%, p = 0.01). The rate of bowel perforation was non-significantly higher in the KP group (8.1%) vs. NoKP group (3.1%, p = 0.11).Conclusions: The sequential strategy including KP and LT allowed performing LT in patients with significant older age and better clinical conditions, when compared to those transplanted without previous KP. Patient and graft survivals were not impacted by previous KP. Although previous KP was associated with an increased rate of post-LT surgical complications, bowel perforation and bleeding did not occur significantly more frequently. Such results support the current strategy based on sequential treatment.

Learning over No-Preferred and Preferred Sequence of Items for Robust Recommendation

In this paper, we propose a theoretically supported sequential strategy for training a large-scale Recommender System (RS) over implicit feedback, mainly in the form of clicks. The proposed approach consists in minimizing pairwise ranking loss over blocks of consecutive items constituted by a sequence of non-clicked items followed by a clicked one for each user. We present two variants of this strategy where model parameters are updated using either the momentum method or a gradient-based approach. To prevent updating the parameters for an abnormally high number of clicks over some targeted items (mainly due to bots), we introduce an upper and a lower threshold on the number of updates for each user. These thresholds are estimated over the distribution of the number of blocks in the training set. They affect the decision of RS by shifting the distribution of items that are shown to the users. Furthermore, we provide a convergence analysis of both algorithms and demonstrate their practical efficiency over six large-scale collections with respect to various ranking measures and computational time.

Head-to-Head Evaluation of Five Automated SARS-CoV-2 Serology Immunoassays in Various Prevalence Settings

Purpose: To assess the diagnostic performances of five automated anti-SARS-CoV-2 immunoassays, Epitope (N), Diasorin (S1/S2), Euroimmun (S1), Roche N (N), and Roche S (S-RBD), and to provide a testing strategy based on pre-test probability. Methods: We assessed the receiver operating characteristic (ROC) areas under the curve (AUC) values, along with the sensitivity, specificity, positive predictive values (PPVs), and negative predictive values (NPVs), of each assay using a validation sample set of 172 COVID-19 sera and 185 negative controls against a validated S1-immunofluorescence as a reference method. The three assays displaying the highest AUCs were selected for further serodetection of 2033 sera of a large population-based cohort. Results: In the validation analysis (pre-test probability: 48.1%), Roche N, Roche S and Euroimmun showed the highest discriminant accuracy (AUCs: 0.99, 0.98, and 0.98) with PPVs and NPVs above 96% and 94%, respectively. In the population-based cohort (pre-test probability: 6.2%) these three assays displayed AUCs above 0.97 and PPVs and NPVs above 90.5% and 99.4%, respectively. A sequential strategy using an anti-S assay as screening test and an anti-N as confirmatory assays resulted in a 96.7% PPV and 99.5% NPV, respectively. Conclusions: Euroimmun and both Roche assays performed equally well in high pre-test probability settings. At a lower prevalence, sequentially combining anti-S and anti-N assays resulted in the optimal trade-off between diagnostic performances and operational considerations.

Selective Terminal Functionalization of Linear Alkanes

Selective undirected functionalization of strong primary C-H bonds of linear alkanes, that do not possess directing groups, historically stands as one of the most challenging transformation in chemistry. In this Article, we report a two-step sequential strategy involving a biocatalytic dehydrogenation / remote hydrofunctionalization, as a unified and versatile approach to selectively convert linear alkanes into a large array of valuable functionalized aliphatic derivatives. The dehydrogenation is carried out by a mutant strain of Rhodococcus and the produced alkenes are subsequently engaged in a remote functionalization through a metal-catalyzed hydrometalation/migration sequence that subsequently react with a large variety of electrophiles. The judicious implementation of this combined biocatalytic and organometallic approach enabled us to develop a high-yielding protocol to site-selectively functionalize unreactive primary C–H bonds.

Modeling sequential systemic therapy for unresectable hepatocellular carcinoma in the era of immunotherapy: What comes next?

324 Background: Atezolizumab plus Bevacizumab represents the new best performing first-line approach for unresectable hepatocellular carcinoma (u-HCC). However, the best sequential strategy after every first-line failure (for progression or intolerance) remains elusive, and options for retreating patients failing Atezolizumab plus Bevacizumab with multi-kinase inhibitors (MKI) or immune checkpoint inhibitor (ICI) are yet undefined. Methods: We developed a Markov model to analyze simulated-Overall Survival (s-OS) of second-line ICIs or MKIs after first-line Atezolizumab plus Bevacizumab over a lifetime horizon. For first-line therapy, PFS of Atezolizumab plus Bevacizumab was extracted from Imbrave 150 trial and it was used as endpoint since it is not influenced by post-progression survival. For second-line retreatment, pooled OS of MKIs (Regorafenib and Cabozantinib), or ICIs (Nivolumab and Pembrolizumab) were adopted. Survival estimates for sequential settings considered the proportion of patients who did not receive second-line therapy due to death during first-line therapy. Individual patient survival data were extracted from PFS and OS Kaplan-Meier curves of RESORCE trial for Regorafenib, CELESTIAL trial for Cabozantinib, CheckMate-040 for Nivolumab and Keynote-240 for Pembrolizumab. Each reconstructed survival curve was inspected for accuracy and was compared with originally published curves. Results: First-line Atezolizumab plus Bevacizumab followed by second-line ICIs turned on from the model as the best sequential strategy (median s-OS 24 months; 95% Confidence Interval (CI) 23-26 months) and extends survival when compared Atezolizumab plus Bevacizumab followed by MKIs (median s-OS 20 months; 95% CI 19-21 months). Conclusions: To our knowledge and given the absence of adequately designed sequential RCTs, this is the first model to date which suggests, with a proper methodological approach, an accurate estimate of outcome of patients with u-HCC treated by sequential systemic therapies. In patients with u-HCC failing first-line treatment, modelling estimates of s-OS for each retreatment strategies may assist in choosing the most promising sequences in order to plan appropriate RCTs.

The Product Quality, Impacts, and Implication of Solo Batik Carnival Event on Solo City’s Spatial Guidelines

Solo Batik Carnival (SBC) is an annual carnival event which have vision to develop creative industry base on batik and reusable products to increase the value as artistic artwork masterpieces, held in Solo by Surakarta Tourism Office as the vice of regional goverment collaborate with Yayasan Solo Batik Carnival. The main purpose of this event are to introduce batik as a legacy of Java culture, and make Solo as one of tourist destination esspecially in fashion interest with the aims in educational development, art, culture, and economic increasing. Therefore, this study is so important and necessary to figure out about: (a) dependability of event quality and spatial in city’s space study, and (b) correlation between impact to the community and the city’s ability to coverage activities during event. This research used sequential mixed methods theory with exploratory sequential strategy. Explorative method used for exploration on field and made a qualitative analysis to find the facts, and compare it with quantitative data from local and tourists respondents with two audiences: zone, tribune and runway. It takes event quality, economic, social and culture impact, and also open public space elements as indicators of research. Thereby the results of this research: first, SBC has a potential ability as an attraction. Second, SBC has a value to increase and develop community economic conditions and also put the city on the national tourism position with creating image identity. And third, event quality and the event’s impacts have certainly been references to design guide-lines of the city’s space surrounding the event’s area.

Feasibility of bioethanol production from rice bran

Rice bran is a by-product of rice production with a high carbohydrate and starch content and the potential for bioethanol production by alcoholic fermentation. This article describes bioethanol production by Saccharomyces cerevisiae from hydrolyzed defatted rice bran (DRB) a rice by-product applying ultrasonic treatment and protease addition, as well as a sequential strategy of experimental design (SEED). In the first Central Composite Rotatable Design (CCRD), the temperature (25-30 °C) and inoculum concentration (0.5-50 g L-1) had positive effects on bioethanol production, while the effect of pH (4.0-6.0) was not significant. In the second CCRD, the temperature (28-35 °C) and inoculum concentration (10-70 g L-1) had negative and positive effects on bioethanol production (p < 0.05). Protease addition (15 µL g-1) increased the conversion of substrate into bioethanol by 76%. The optimized conditions for the production of 40.7 g L-1 bioethanol were a temperature of 31.5 °C and an inoculum concentration of 70 g L-1. Validation in a benchtop bioreactor produced 40.0 g L-1 of bioethanol from hydrolyzed DRB, and the SEED was characterized as a useful tool to improve bioethanol production from DRB. Furthermore, the DRB proved to be a by-product with great potential for bioethanol production, derived from alternative sources not commonly used in human food.

Sequential Strategy Including FFRCT Plus Stress-CTP Impacts on Management of Patients with Stable Chest Pain: The Stress-CTP RIPCORD Study

Stress computed tomography perfusion (Stress-CTP) and computed tomography-derived fractional flow reserve (FFRCT) are functional techniques that can be added to coronary computed tomography angiography (cCTA) to improve the management of patients with suspected coronary artery disease (CAD). This retrospective analysis from the PERFECTION study aims to assess the impact of their availability on the management of patients with suspected CAD scheduled for invasive coronary angiography (ICA) and invasive FFR. The management plan was defined as optimal medical therapy (OMT) or revascularization and was recorded for the following strategies: cCTA alone, cCTA+FFRCT, cCTA+Stress-CTP and cCTA+FFRCT+Stress-CTP. In 291 prospectively enrolled patients, cCTA+FFRCT, cCTA+Stress-CTP and cCTA+FFRCT+Stress-CTP showed a similar rate of reclassification of cCTA findings when FFRCT and Stress-CTP were added to cCTA. cCTA, cCTA+FFRCT, cCTA+Stress-CTP and cCTA+FFRCT+Stress-CTP showed a rate of agreement versus the final therapeutic decision of 63%, 71%, 89%, 84% (cCTA+Stress-CTP and cCTA+FFRCT+Stress-CTP vs cCTA and cCTA+FFRCT: p < 0.01), respectively, and a rate of agreement in terms of the vessels to be revascularized of 57%, 64%, 74%, 71% (cCTA+Stress-CTP and cCTA+FFRCT+Stress-CTP vs cCTA and cCTA+FFRCT: p < 0.01), respectively, with an effective radiation dose (ED) of 2.9 ± 1.3 mSv, 2.9 ± 1.3 mSv, 5.9 ± 2.7 mSv, and 3.1 ± 2.1 mSv. The addition of FFRCT and Stress-CTP improved therapeutic decision-making compared to cCTA alone, and a sequential strategy with cCTA+FFRCT+Stress-CTP represents the best compromise in terms of clinical impact and radiation exposure.