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Max wants to be an artist like Arthur, but his first attempt at using a paintbrush sends the two friends on a whirlwind trip through various media, with unexpected consequences.

Background Amatoxin-related acute liver failure (AT-ALF) carries high mortality without liver transplantation (LTX). While therapeutic plasma exchange (PEX) might improve LTX-free survival in other ALF cases, its role in AT-ALF is unclear. Clinical practice varies, and, given the rarity of this ALF entity, the feasibility of conducting a randomized controlled trial to investigate PEX in AT-ALF is more or less impossible. Methods The Amanita-PEX study is a multi-center, international, retrospective study analyzing patients with AT-ALF from 2013 to 2024. The primary outcome was 28-day LTX-free survival (composite endpoint: death or LTX) after ALF diagnosis. Results The study included 111 patients from 25 centers: 82 received standard-of-care (SOC), and 29 received at least one PEX-session. PEX and SOC-groups were comparable at baseline, but 76% of PEX- vs. 58% of SOC-patients developed hepatic-encephalopathy (HE) grade ≥ 2 ( p  = 0.021). While the primary outcome of 28-day LTX-free survival in all patients was not different between the SOC and PEX-groups, in the subgroup of patients with maximal HE grade ≥ 2, LTX-free survival was 19.1% ( n  = 8/42) in the SOC group, while it was 36.4% ( n  = 8/22) in patients receiving adjunctive PEX (Gehan-Breslow-Wilcoxon- p  = 0.041, Log-Rank- p  = 0.060). PEX was independently associated with reduced risk of the combined endpoint death or liver transplantation within 28 days from inclusion in patients with HE grade ≥ 2 (HR 0.37, 95%-CI 0.19–0.73, p  = 0.004). After propensity-score-matching, LTX-free survival was 28% in the SOC- and 52% in the PEX group (Gehan-Breslow- p  = 0.036; Log-Rank- p  = 0.035). Conclusions In this real-world study, adjunctive use of PEX was associated with increased LTX-free-survival in patients with AT-ALF and HE grade ≥ 2. Highlights Acute liver failure due to ingestion of mushrooms containing amatoxins has a poor prognosis when higher grade hepatic encephalopathy develops. Adjunctive use of therapeutic plasma exchange was independently associated with increased liver transplant-free-survival in patients with amatoxin associated acute liver failure and maximum hepatic encephalopathy grade ≥ 2. Therapeutic plasma exchange was not associated with increased liver transplant-free-survival in patients with hepatic encephalopathy grade 1 and did not improve overall-survival or other secondary endpoints such as shorter length of hospital stay or lower incidence of acute kidney injury, need for renal-replacement therapy, invasive ventilation or vasopressor support. Impact and Implications Therapeutic plasma exchange is frequently used in the management of patients with acute liver failure but its effect on improving liver transplant-free-survival has recently been questioned. Amatoxin-associated acute liver failure is a rare entity of acute liver failure and solid data concerning clinical outcomes are scarce. This multi-national, multi-center, real-world, retrospective study suggests that therapeutic plasma exchange is significantly associated with improved liver transplant-free survival only in patients with amatoxin-associated acute liver failure and higher-grade hepatic encephalopathy. These results might help to guide the future use of therapeutic plasma exchange in this specific patient population. Graphical abstract

Data-driven cell tracking and segmentation methods in biomedical imaging require diverse and information-rich training data. In cases where the number of training samples is limited, synthetic computer-generated data sets can be used to improve these methods. This requires the synthesis of cell shapes as well as corresponding microscopy images using generative models. To synthesize realistic living cell shapes, the shape representation used by the generative model should be able to accurately represent fine details and changes in topology, which are common in cells. These requirements are not met by 3D voxel masks, which are restricted in resolution, and polygon meshes, which do not easily model processes like cell growth and mitosis. In this work, we propose to represent living cell shapes as level sets of signed distance functions (SDFs) which are estimated by neural networks. We optimize a fully-connected neural network to provide an implicit representation of the SDF value at any point in a 3D+time domain, conditioned on a learned latent code that is disentangled from the rotation of the cell shape. We demonstrate the effectiveness of this approach on cells that exhibit rapid deformations (Platynereis dumerilii), cells that grow and divide (C. elegans), and cells that have growing and branching filopodial protrusions (A549 human lung carcinoma cells). A quantitative evaluation using shape features and Dice similarity coefficients of real and synthetic cell shapes shows that our model can generate topologically plausible complex cell shapes in 3D+time with high similarity to real living cell shapes. Finally, we show how microscopy images of living cells that correspond to our generated cell shapes can be synthesized using an image-to-image model.

Methods allowing the synthesis of realistic cell shapes could help generate training data sets to improve cell tracking and segmentation in biomedical images. Deep generative models for cell shape synthesis require a light-weight and flexible representation of the cell shape. However, commonly used voxel-based representations are unsuitable for high-resolution shape synthesis, and polygon meshes have limitations when modeling topology changes such as cell growth or mitosis. In this work, we propose to use level sets of signed distance functions (SDFs) to represent cell shapes. We optimize a neural network as an implicit neural representation of the SDF value at any point in a 3D+time domain. The model is conditioned on a latent code, thus allowing the synthesis of new and unseen shape sequences. We validate our approach quantitatively and qualitatively on C. elegans cells that grow and divide, and lung cancer cells with growing complex filopodial protrusions. Our results show that shape descriptors of synthetic cells resemble those of real cells, and that our model is able to generate topologically plausible sequences of complex cell shapes in 3D+time.

Edward Genocchio, Michelle Lee and David Müller-Wiesner of Spruson & Ferguson consider the options for protecting visually distinctive fine-dining endeavours with IP

Professor Sipe gives a wonderfully thorough overview of the world of the picturebook. I would like to draw attention to one aspect of the picturebook that is so obvious as to be taken for granted-its length. The brevity of the picturebook lets children easily hold the complete story experience in their minds. The limited length also lets me, as an author and illustrator, have a vision of the book as a whole in my mind throughout the creation process.

This study examined the mediating role of anxiety in the self-reports of somatic complaints in 96 depressed adolescent inpatients. Sixty-four subjects with major depressive episodes and comorbid anxiety disorders (MDE-A) determined from the Diagnostic Interview for Children and Adolescents--Revised (DICA-R) reported significantly more somatic complaints than 32 adolescents having major depressive episodes without comorbid anxiety (MDE). An analysis of covariance demonstrated that, with anxiety symptoms controlled, MDE and MDE-A groups did not differ significantly in somatic complaints. A hierarchical multiple-regression analysis revealed that, with demographic and anxiety symptoms controlled, depressive symptoms did not contribute to the explanation or prediction of somatic complaints. The results suggest that anxious, but not depressive symptoms, are independently associated with somatic complaints. The results are discussed in light of new affective models of psychopathology.

David Wiesner, winner of the 2002 Caldecott Medal for his children's book \"The Three Pigs,\" is profiled. Wiesner has a unique style of visual storytelling that immediately grabs readers' attention and plunges them into whatever fantasy realm he has created.

Wiesner talks about how to read a wordless picture book. You read the pictures--and there are no air quotes around the word read. The pictures are the language and they must be read as carefully as any book with text. When an artist removes the text, they invite readers to decode the pictures for themselves, so every child reads the book in their own unique way according to their own personal life experiences and background. A wordless (or almost wordless) picture book asks children to collaborate in the storytelling process--a very empowering request.