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9, better than all in silico predictors tested. Combining this algorithm with other in silico approaches can further increase performance, reaching an AUC of 0.94. This study expands our understanding of HPP heterogeneity and genotype/phenotype relationships with the aim of improving clinical ALPL variant interpretation. © 2020 The Authors. Human Mutation published by Wiley Periodicals, Inc.Beside sensing and delivery, another peculiar property arising from confinement in discrete molecular hosts comes from the possibility to have in close proximity, and in defined position, two different molecules (hetero co-encapsulation). This phenomenon can be tuned considering steric and electronic properties of the guests. In this work, a study on the parameters affecting homo and hetero co-encapsulation processes within a supramolecular cage is reported. In particular, different benzoate guests were bound within a supramolecular cage containing two metal binding sites and the experimental binding thermodynamics measured. Unexpectedly, from competition experiments we observed that the maximum concentration of hetero co-encapsulation is achieved if a weakly binding guest is used to partially displace a strongly binding guest. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Increasing the stream of recycled plastic from currently 12 wt.% necessitates an approach beyond traditional low value recycling via melting and re-extrusion. Various chemical recycling processes have great potential to enhance recycling rates, because a higher variety of plastic waste streams can be recycled leading to a higher purity and quality product than melting and re-extrusion. But despite long-standing efforts, commercial processes are still not operated at the volumes to address the recycling necessity. In this review, a summary of the various chemical recycling routes and assessment via life cycle analysis is complemented by a list of processes developed by companies active in chemical recycling. We show that each of the currently available processes is applicable for specific plastic waste streams. Thus, only a combination of different technologies can address the plastic waste problem. While pyrolysis can handle relatively mixed waste streams, it works best with polyolefins, PS and PMMA. Contaminations including PVC, PET and PU and non-plastic additives like glass fiber cause operational problems. Multilayer plastics containing these materials are best separated into mono-streams by dissolution/precipitation. Pure polyester or polyamide waste streams can be recycled by solvolysis techniques with high monomer recovery. Research should focus on more realistic, more contaminated and mixed waste streams, while collection and sorting infrastructure will need to be improved, i.e. by stricter regulation. This review aims to inspire both science and innovation for the production of higher value and quality products from plastic recycling suitable for reuse or valorization to create the necessary economic and environmental push for a circular economy. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Excessive growth of microalgae due to use of fertilizers, detergents, and discharge of domestic waste results in the eutrophication and degradation of the water quality of lakes and ponds. Conteltinib purchase The present study aimed to improve the quality of pond water by harvesting mixed cultures of microalgae grown in a pond using moringa oleifera (MO) extract as a coagulant. The study comprises evaluating the effects of coagulant dose, pH, mixing time, mixing rate, settling time, temperature and algal biomass concentration on nutrients and microalgae cells removal. The pond water quality restoration was assessed by characterisation of raw and MO treated water. The MO was found to be very effective for mixed culture microalgae harvesting with flocculation efficiency of 92.97% at dose of 15 ml/L of MO extract, pH 8, mixing time 5 min, mixing rate 30 rpm and 20 min settling time. The results have shown significant improvement in pond water quality with reduction in turbidity from 388.16 ± 48.23 to 8.39 ± 1.0 NTU, chlorophyll-a from 635.01 ± 86.20 to 15.03 ± 1.5 mg/m3 , total nitrogen (TN) from 20.37 ± 4.64 to 12.10 ± 1.19 mg/L and total phosphorus (TP) from 2.05 ± 0.10 to 1.61 ± 0.24 mg/L. This article is protected by copyright. All rights reserved.We developed a new method for conditional regulation of CRISPR/Cas9 activity in mammalian cells and zebrafish embryos via photochemically activated, caged guide RNAs. Caged gRNAs are generated by substituting four nucleobases evenly distributed throughout the 5'-protospacer region with caged nucleobases during synthesis. Caging confers complete suppression of gRNAdsDNA- target hybridization and rapid restoration of CRISPR/Cas9 function upon optical activation. This tool offers simplicity and complete programmability in design, high spatiotemporal specificity in cells and zebrafish embryos, excellent off to on switching, and stability by preserving the ability to form Cas9gRNA ribonucleoprotein complexes. Caged gRNAs are novel tools for conditional control of gene editing, thereby enabling the investigation of spatiotemporally complex physiological events by obtaining a better understanding of dynamic gene regulation. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.BACKGROUND Preschool children with recurrent wheezing suffer high morbidity. It is unclear whether objective measures of asthma control, such as pulmonary function tests (PFTs), provide additional information to the clinical assessment. METHODS We recruited children between 3-6 years old, with a history of recurrent wheezing in the preceding year and treated for acute wheezing exacerbation in the Emergency Department (ED) into an observational cohort study. Children attended two outpatient visits the first study visit within five days of discharge from the ED and the second study visit 12 weeks after the ED visit. We performed standardized symptom score (Test for Respiratory and Asthma Control in Kids (TRACK)), multiple breath washout (MBW), spirometry, and clinical assessment at both visits. RESULTS Seventy-four children, mean (standard deviation (SD)) age 4.32 years (0.84), attended both visits. Paired FEV0.75 and LCI measurements at both time points were obtained in 37 and 34 subjects respectively. Feasibility for all tests improved at visit 2 and was not age dependent. At the second study visit, a third had controlled asthma based on the TRACK score, and the mean lung clearance index (LCI) improved from 9.86 to 8.31 (p = 0.003); however, 46% had an LCI in the abnormal range. FEV0.75 z-score improved from -1.66 to -1.17 (p = 0.05) but remained in the abnormal range in 24%. LCI was abnormal in more than half of the children with "well-controlled" asthma based on the TRACK score. There was no correlation between PFT measures and TRACK scores at either visit. CONCLUSIONS LCI demonstrates a persistent deficit post-exacerbation in a large proportion of preschoolers with recurrent wheezing, highlighting that symptom scores alone may not suffice for monitoring these children. This article is protected by copyright. All rights reserved.Primary localized cutaneous amyloidosis (PLCA) is a recalcitrant sporadic dermatological condition and most treatments have failed so far. We studied the efficacy of topical dimethyl sulfoxide (DMSO) 50% solution in comparison with tretinoin 0.5% cream in treatment of macular amyloidosis. In this split-side within-person single-blinded randomized clinical trial, 18 patients with bilateral macular amyloidosis received topical DMSO 50% solution and tretinoin 0.5% cream either on their right or the left side. The colorimetry, pruritus scoring, and photography were done. A significant pigmentation decline per each follow-up was observed in DMSO group compared to the tretinoin group (tretinoin -1.31 vs DMSO -7.34; difference in slopes -6.03 [95% confidence interval -12.06 to -0.01], PInteraction = .049). An insignificant diminution trend in pigmentation was observed for both treatments (Ptretinoin = .672, PDMSO = .092). Also, both treatments relived itchiness, but DMSO completely dispatched itchiness from the first follow-up (P = .003 for tretinoin and less then .0001 for DMSO). In conclusion, our results showed DMSO and tretinoin cream have the positive effect on the both pigmentation and itchiness in PLCA. DMSO may be more beneficial than tretinoin, since DMSO was significantly better in reducing itchiness. More investigations are warranted to provide sufficient evidence. © 2020 Wiley Periodicals, Inc.Frustrated Lewis pairs consisting of diphenylphosphino and boryl groups located at the ortho-position can trap difluorocarbene affording stable zwitterionic adducts. The reaction can be reversed to release difluorocarbene at elevated temperatures. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.Dye-sensitized solar cells (DSSCs) based on Cu(II/I) bipyridyl or phenanthroline complexes as redox shuttles have achieved very high open-circuit voltages ( V OC , > 1 V). However, their short-circuit photocurrent density ( J SC ) has remained modest. The challenge for increasing the J SC is expected to extend the spectral response of sensitizers to the red or NIR region while maintaining efficient electron injection in the mesoscopic TiO 2 film and fast regeneration by the Cu(I) complex. Here, we report two new D-A-π-A featured sensitizers coded HY63 and HY64 , which employ either benzothiadiazole (BT) or phenanthrene-fused-quinoxaline (PFQ) as the auxiliary electron-withdrawing acceptor moiety. In spite of very similar energy levels and absorption onsets, HY64 -based DSSCs outperform largely their HY63 counterpart, achieving an outstanding power conversion efficiency (PCE) of 12.5% with superior stability. In depth studies of interfacial charge carrier dynamics show that PFQ is superior to BT in retarding charge recombination resulting in near quantitative collection of photogenerated charge carriers. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.The long-term efficacy of nivolumab in esophageal squamous cell carcinoma and its association with disease biomarkers are currently not well known. Therefore, we investigated the association in Japanese patients with treatment-refractory advanced esophageal cancer who participated in an open-label, single-arm, multicenter phase 2 study. Patients received nivolumab 3 mg/kg, intravenously every 2 weeks until disease progression or unacceptable toxicity, and were followed up for 2 years after the initial dosing of the last patient. Tissue samples were collected before treatment, and analyzed for PD-L1, CD8+ of tumor and tumor infiltrating lymphocytes (TILs) and HLA class 1. Efficacy endpoints included objective response rate (ORR), overall survival (OS), progression-free survival (PFS), time to response and duration of response. Of 65 enrolled patients (83% male), 64 were evaluable for efficacy and 41 (63%) for biomarkers. The ORR, median OS, and survival rate were 17.2%, 10.78 months, and 17.2%, respectively. Time to response was 1.45 months and duration of response was 11.17 months. PD-L1 positivity of tumor cell was possibly associated with better PFS (2.04 vs 1.41 months, cut-off 1%) and OS (11.33 vs 6.24 months, cut-off 1%). Median OS was prolonged in patients with a median number of TILs >63.75% versus ≤63.75% (11.33 vs 7.85 months). Nivolumab demonstrated continued long-term efficacy, as seen by the stability of PFS and OS, in Japanese patients with esophageal squamous cell carcinoma. Further investigation of PD-L1 tumor expression and TILs as potential biomarkers for predicting patients likely to benefit from nivolumab therapy is warranted. This article is protected by copyright. All rights reserved.

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