Rituximab or Cyclophosphamide in the Treatment of Membranous Nephropathy: The RI-CYCLO Randomized Trial

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A Quantitative Comparison of Physical Accuracy and Numerical Stability of Lattice Boltzmann Color Gradient and Pseudopotential Multicomponent Models for Microfluidic Applications

The performances of the Color-Gradient (CG) and the Shan-Chen (SC) multicomponent Lattice Boltzmann models are quantitatively compared side-by-side on multiple physical flow problems where breakup, coalescence and contraction of fluid ligaments are important. The flow problems are relevant to microfluidic applications, jetting of microdroplets as seen in inkjet printing, as well as emulsion dynamics. A significantly wider range of parameters is shown to be accessible for CG in terms of density-ratio, viscosity-ratio and surface tension values. Numerical stability for a high density ratio $\mathcal{O}(1000)$ is required for simulating the drop formation process during inkjet printing which we show here to be achievable using the CG model but not using the SC model. Our results show that the CG model is a suitable choice for challenging simulations of droplet formation, due to a combination of both numerical stability and physical accuracy. We also present a novel approach to incorporate repulsion forces between interfaces for CG, with possible applications to the study of stabilized emulsions. Specifically, we show that the CG model can produce similar results to a known multirange potentials extension of the SC model for modelling a disjoining pressure, opening up its use for the study of dense stabilized emulsions.     

Biallelic loss of function variants in PPP1R21 cause a neurodevelopmental syndrome with impaired endocytic function

Next‐generation sequencing (NGS) has been instrumental in solving the genetic basis of rare inherited diseases, especially neurodevelopmental syndromes. However, functional workup is essential for precise phenotype definition and to understand the underlying disease mechanisms. Using whole exome (WES) and whole genome sequencing (WGS) in four independent families with hypotonia, neurodevelopmental delay, facial dysmorphism, loss of white matter, and thinning of the corpus callosum, we identified four previously unreported homozygous truncating PPP1R21 alleles: c.347delT p.(Ile116Lysfs*25), c.2170_2171insGGTA p.(Ile724Argfs*8), c.1607dupT p.(Leu536Phefs*7), c.2063delA p.(Lys688Serfs*26) and found that PPP1R21 was absent in fibroblasts of an affected individual, supporting the allele's loss of function effect. PPP1R21 function had not been studied except that a large scale affinity proteomics approach suggested an interaction with PIBF1 defective in Joubert syndrome. Our co‐immunoprecipitation studies did not confirm this but in contrast defined the localization of PPP1R21 to the early endosome. Consistent with the subcellular expression pattern and the clinical phenotype exhibiting features of storage diseases, we found patient fibroblasts exhibited a delay in clearance of transferrin‐488 while uptake was normal. In summary, we delineate a novel neurodevelopmental syndrome caused by biallelic PPP1R21 loss of function variants, and suggest a role of PPP1R21 within the endosomal sorting process or endosome maturation pathway.     

The independency of the Bereitschaftspotential from previous stimulus‐locked P3 in visuomotor response tasks

The Bereitschaftspotential (BP) and the P3 are well‐known ERPs usually observed during self‐paced and externally triggered tasks. Recently, the BP was also detected in externally triggered tasks before stimulus onset. However, doubts have been raised about the authenticity of the BP in these tasks due to possible overlaps with the previous trial P3 (hereinafter s‐1 P3). Here, we aim to test the authenticity of the BP in externally triggered tasks by comparing ERPs obtained during two visuomotor response tasks with different interstimulus intervals (ISIs) allowing (short‐ISI; 1,000–2,000 ms) or not (long‐ISI; 2,000–4,000 ms) P3‐BP overlaps. In line with previous research, we hypothesize that BP and the s‐1 P3 contribute independently to the scalp‐detected activities during these tasks. ERPs were recorded from 14 healthy participants during the short‐ISI and long‐ISI visuomotor response tasks. Amplitudes and latencies of pre‐ (BP and pN) and poststimulus ERP components (P1, pN1, pP1, N1, pP2, dpP2, N2, P3) were compared between conditions. No effect of ISI was found on the amplitude of any pre‐ and poststimulus components. In contrast, longer ISI is associated with earlier onsets of the BP and pN components. In visuomotor response tasks, the BP is independent from the P3 elicited by the previous trial (s‐1 P3), even using relatively short ISI. Since the different ISIs did not affect the amplitude of the BP and the P3 components, we conclude that also a short ISI can be adopted safely and conveniently to keep a reasonable duration of the overall experiment.     

Mandible strength and geometry in relation to bite force: a study in three caviomorph rodents

The monophyletic group Caviomorpha constitutes the most diverse rodent clade in terms of locomotion, ecology and diet. Caviomorph species show considerable variation in cranio‐mandibular morphology that has been linked to the differences in toughness of dietary items and other behaviors, such as chisel‐tooth digging. This work assesses the structural strength of the mandible of three caviomorph species that show remarkable differences in ecology, behavior and bite force: Chinchilla lanigera (a surface‐dwelling species), Octodon degus (a semi‐fossorial species) and Ctenomys talarum (a subterranean species). Finite element (FE) models of the mandibles are used to predict the stresses they withstand during incisor biting; the results are related to in vivo bite forces and interspecific variations in the mandibular geometries. The study concludes that the mandible of C. talarum is better able to withstand strong incisor bites. Its powerful adducting musculature is consistent with the notorious lateral expansion of the angular process and the masseteric crest, and the enhanced cortical bone thickness. Although it has a relatively low bite force, the mandible of O. degus also shows a good performance for mid‐to‐strong incisor biting, in contrast to that of C. lanigera, which exhibits, from a mechanical point of view, the worst performance. The mandibles of C. talarum and O. degus appear to be better suited to withstand stronger reaction forces from incisor biting, which is consistent with their closer phylogenetic affinity and shared digging behaviors. The contrast between the low in vivo bite force of C. lanigera and the relatively high estimations that result from the models suggests that its adductor musculature could play significant roles in functions other than incisor biting.     

Acute Toxicity of Ammonia,Nitrite and Nitrate to Shrimp <Emphasis Type="Italic">Litopenaeus vannamei</Emphasis> Postlarvae in Low-Salinity Water

Shrimp farming in low salinities waters is an alternative to increasing production, and counteracting disease problems in brackish and marine waters. However, in low-salinity waters, toxicity of nitrogen compounds increases, and there is no available data of its acute toxicity in shrimp postlarvae. This study determined the acute toxicity of ammonia, nitrite and nitrate in Litopenaeus vannamei postlarvae in 1 and 3 g/L salinity, as well as the safety levels. The LC₅₀ confirms that nitrite is more toxic than ammonia and nitrate in low salinity waters, and that its toxicity increases with a decrease in salinity. The safe levels estimated for salinities of 1 and 3 g/L were 0.54 and 0.81 mg/L for total ammonia–N, 0.17 and 0.25 mg/L for NO₂–N, and 5.6 and 21.5 mg/L for NO₃–N, respectively.     

Accuracy of computerized tomography for the evaluation of mandibular sites prior to implant placement

The objective of the present study was to observe the effect of positioning of the mandible on the accuracy of cross-sectional images obtained by reformatting computerized tomographic (CT) scans. An additional aim was to evaluate the ability of a software program (DentalVox, Era Scientific) to reconstruct these measurements on the reformatted images, regardless of the positioning of the mandible, accurately and without distortion. The test was carried out by examining a partially edentulous dry human mandible with an acrylic radiologic template. Through the use of an acrylic glass support, the mandible was positioned at angles of 0, 10, 15, 20, and 30 degrees relative to the scanning gantry, and a series of CT scans was performed that provided five sets of axial images. Each set of original axial images was reformatted by the DentalVox software, used first in its basic function, which is typical of all software for axial CT measurement (control group), and again in its function of site-specific multiplanar reconstruction (test group). The results showed that the position of the mandible in relation to the CT gantry can influence the precision of the linear measurements. The error ranged from 2% to 51%. The DentalVox software allowed the reconstruction of cross-sectional images with very little distortion regardless of the mandibular position.