Rapid prediction of lab-grown tissue properties using deep learning

The interactions between cells and the extracellular matrix are vital for the self-organisation of tissues. In this paper we present proof-of-concept to use machine learning tools to predict the role of this mechanobiology in the self-organisation of cell-laden hydrogels grown in tethered moulds. We develop a process for the automated generation of mould designs with and without key symmetries. We create a large training set with $N=6500$ cases by running detailed biophysical simulations of cell-matrix interactions using the contractile network dipole orientation (CONDOR) model for the self-organisation of cellular hydrogels within these moulds. These are used to train an implementation of the \texttt{pix2pix} deep learning model, reserving $740$ cases that were unseen in the training of the neural network for training and validation. Comparison between the predictions of the machine learning technique and the reserved predictions from the biophysical algorithm show that the machine learning algorithm makes excellent predictions. The machine learning algorithm is significantly faster than the biophysical method, opening the possibility of very high throughput rational design of moulds for pharmaceutical testing, regenerative medicine and fundamental studies of biology. Future extensions for scaffolds and 3D bioprinting will open additional applications.Comment: 26 Pages, 11 Figure

High-throughput design of cultured tissue moulds using a biophysical model

The technique presented here identifies tethered mould designs, optimised for growing cultured tissue with very highly-aligned cells. It is based on a microscopic biophysical model for polarised cellular hydrogels. There is an unmet need for tools to assist mould and scaffold designs for the growth of cultured tissues with bespoke cell organisations, that can be used in applications such as regenerative medicine, drug screening and cultured meat. High-throughput biophysical calculations were made for a wide variety of computer-generated moulds, with cell-matrix interactions and tissue-scale forces simulated using a contractile-network dipole-orientation model. Elongated moulds with central broadening and one of the following tethering strategies are found to lead to highly-aligned cells: (1) tethers placed within the bilateral protrusions resulting from an indentation on the short edge, to guide alignment (2) tethers placed within a single vertex to shrink the available space for misalignment. As such, proof-of-concept has been shown for mould and tethered scaffold design based on a recently developed biophysical model. The approach is applicable to a broad range of cell types that align in tissues and is extensible for 3D scaffolds

Using Mindfulness for Increasing Provider Capacity to Support Inner City Survivors of Violence [English and Spanish versions]

A Spanish translation of this publication is available to download under Additional Files below. Mindfulness is recognized as an evidence-based practice that can improve a person’s physical and emotional health and well-being. This research project examined the cultural relevance and potential acceptability of mindfulness practices by front-line providers working with a low-income community of color affected by gun homicide

High-throughput design of cultured tissue moulds using a biophysical model: optimising cell alignment

The technique presented here identifies tethered mould designs, optimised for growing cultured tissue with very highly-aligned cells. It is based on a microscopic biophysical model for polarised cellular hydrogels. There is an unmet need for tools to assist mould and scaffold designs for the growth of cultured tissues with bespoke cell organisations, that can be used in applications such as regenerative medicine, drug screening and cultured meat. High-throughput biophysical calculations were made for a wide variety of computer-generated moulds, with cell-matrix interactions and tissue-scale forces simulated using a contractile network dipole orientation model. Elongated moulds with central broadening and one of the following tethering strategies are found to lead to highly-aligned cells: (1) tethers placed within the bilateral protrusions resulting from an indentation on the short edge, to guide alignment (2) tethers placed within a single vertex to shrink the available space for misalignment. As such, proof-of-concept has been shown for mould and tethered scaffold design based on a recently developed biophysical model. The approach is applicable to a broad range of cell types that align in tissues and is extensible for 3D scaffolds

Feasibility and Acceptability of Mindfulness for Survivors of Homicide and Their Providers

PURPOSE: This study uses participatory research methods with survivors of homicide and their service providers to explore the feasibility and acceptability of a culturally adapted mindfulness intervention for stress reduction and resilience in homicide survivors. PROCEDURES: Our mixed methods approach included: (a) previewing a Mindfulness-Based Stress Reduction program with providers and survivors; (b) using their iterative feedback during focus groups to revise the curriculum; and (c) studying the acceptability of the adapted curriculum for survivors through focus group and standardized data collection. FINDINGS: We learned that providers use mindfulness for self-care and both providers and survivors view the approach for survivors as promising. Based on attendance, participation, and focus group data, the adapted curriculum was both feasible and acceptable. Survivors\u27 reports suggested most experienced improved emotion regulation, feelings of empowerment, and better coping. CONCLUSIONS: Culturally adapted mindfulness programs may support healing for homicide survivors and possibly other low-income people of color with significant trauma backgrounds. Further investigation is needed to rigorously assess outcomes and specific effects, both positive and negative, of mindfulness in this and other more diversified populations

Halcyornis toliapicus (aves: Lower Eocene, England) indicates advanced neuromorphology in Mesozoic Neornithes

Our recent X-ray micro computer-tomographic (μCT) investigations of Prophaethon shrubsolei and Odontopteryx toliapica from the Lower Eocene London Clay Formation of England revealed the avian brain to have been essentially modern in form by 55 Ma, but that an important vision-related synapomorphy of living birds, the eminentia sagittalis of the telencephalon, was poorly developed. This evidence suggested that the feature probably appeared close to the end of the Mesozoic. Here we use μCT analysis to describe the endocranium of Halcyornis toliapicus, also from the London Clay Formation. The affinities of Halcyornis have been hotly debated, with the taxon referred to the Charadriiformes (Laridae), Coraciiformes (Alcedinidae, and its own family Halcyornithidae) and most recently that Halcyornithidae may be a possible senior synonym of Pseudasturidae (Pan-Psittaciformes). Unlike Prophaethon and Odontopteryx, the eminentia sagittalis of Halcyornis is strongly developed and comparable to that of living species. Like those London Clay taxa, the eminentia sagittalis occupies a rostral position on the telencephalon. The senses of Halcyornis appear to have been well developed. The length of the cochlear duct of the inner ear indicates a hearing sensitivity within the upper range of living species, and enlarged olfactory lobes suggest a reasonable reliance on sense of smell. The optic nerves were especially well developed which, together with the strong development of the eminentia sagittalis, indicates a high degree of visual specialization in Halcyornis. The advanced development of the eminentia sagittalis further supports a Mesozoic age for the appearance of this structure and associated neural architectural complexity found in extant Aves. The eminentia sagittalis of living Psittaciformes is situated caudally on the telencephalon, making a Pan-Psittaciformes relationship unlikely for Halcyorni

IL-4 Receptor α Is an Important Modulator of IL-4 and IL-13 Receptor Binding: Implications for the Development of Therapeutic Targets

IL-4 is a key cytokine associated with allergy and asthma. Induction of cell signaling by IL-4 involves interaction with its cognate receptors, a complex of IL-4Ralpha with either the common gamma-chain or the IL-13R chain alpha1 (IL-13Ralpha1). We found that IL-4 bound to the extracellular domain of IL-4Ralpha (soluble human (sh)IL-4Ralpha) with high affinity and specificity. In contrast with the sequential mechanism of binding and stabilization afforded by IL-4Ralpha to the binding of IL-13 to IL-13Ralpha1, neither common gamma-chain nor IL-13Ralpha1 contributed significantly to the stabilization of the IL-4:IL-4Ralpha complex. Based on the different mechanisms of binding and stabilization of the IL-4R and IL-13R complexes, we compared the effects of shIL-4Ralpha and an IL-4 double mutein (R121D/Y124D, IL-4R antagonist) on IL-4- and IL-13-mediated responses. Whereas IL-4R antagonist blocked responses to both cytokines, shIL-4Ralpha only blocked IL-4. However, shIL-4Ralpha stabilized and augmented IL-13-mediated STAT6 activation and eotaxin production by primary human bronchial fibroblasts at suboptimal doses of IL-13. These data demonstrate that IL-4Ralpha plays a key role in the binding affinity of both IL-13R and IL-4R complexes. Under certain conditions, shIL-4Ralpha has the potential to stabilize binding IL-13 to its receptor to augment IL-13-mediated responses. Thus, complete understanding of the binding interactions between IL-4 and IL-13 and their cognate receptors may facilitate development of novel treatments for asthma that selectively target these cytokines without unpredicted or detrimental side effects.</p

The Florence Statement on Triclosan and Triclocarban

The Florence Statement on Triclosan and Triclocarban documents a consensus of more than 200 scientists and medical professionals on the hazards of and lack of demonstrated benefit from common uses of triclosan and triclocarban. These chemicals may be used in thousands of personal care and consumer products as well as in building materials. Based on extensive peer-reviewed research, this statement concludes that triclosan and triclocarban are environmentally persistent endocrine disruptors that bioaccumulate in and are toxic to aquatic and other organisms. Evidence of other hazards to humans and ecosystems from triclosan and triclocarban is presented along with recommendations intended to prevent future harm from triclosan, triclocarban, and antimicrobial substances with similar properties and effects. Because antimicrobials can have unintended adverse health and environmental impacts, they should only be used when they provide an evidence-based health benefit. Greater transparency is needed in product formulations, and before an antimicrobial is incorporated into a product, the long-term health and ecological impacts should be evaluated

Maraviroc Concentrates in the Cervicovaginal Fluid and Vaginal Tissue of HIV-Negative Women

To compare single- and multiple-dose maraviroc exposures in cervicovaginal fluid (CVF) and vaginal tissue (VT) with blood plasma (BP) and quantify maraviroc protein binding in CVF

Empathy and emotion recognition in people with autism, first-degree relatives, and controls

Empathy is the lens through which we view others' emotion expressions, and respond to them. In this study, empathy and facial emotion recognition were investigated in adults with autism spectrum conditions (ASC; N=314), parents of a child with ASC (N=297) and IQ-matched controls (N=184). Participants completed a self-report measure of empathy (the Empathy Quotient [EQ]) and a modified version of the Karolinska Directed Emotional Faces Task (KDEF) using an online test interface. Results showed that mean scores on the EQ were significantly lower in fathers (p0.05) of children with ASC compared to controls, whilst both males and females with ASC obtained significantly lower EQ scores (p0.05). Finally, results indicated significant differences between males and females with ASC for emotion recognition performance (p0.05). These findings suggest that self-reported empathy deficits in fathers of autistic probands are part of the 'broader autism phenotype'. This study also reports new findings of sex differences amongst people with ASC in emotion recognition, as well as replicating previous work demonstrating empathy difficulties in adults with ASC. The use of empathy measures as quantitative endophenotypes for ASC is discussed