Machine Learning for Health: Algorithm Auditing & Quality Control.

Developers proposing new machine learning for health (ML4H) tools often pledge to match or even surpass the performance of existing tools, yet the reality is usually more complicated. Reliable deployment of ML4H to the real world is challenging as examples from diabetic retinopathy or Covid-19 screening show. We envision an integrated framework of algorithm auditing and quality control that provides a path towards the effective and reliable application of ML systems in healthcare.

Long-term in vivo imaging reveals tumor-specific dissemination and captures host tumor interaction in zebrafish xenografts.

Understanding mechanisms mediating tumor metastasis is crucial for diagnostic and therapeutic targeting. Here, we take advantage of a transparent embryonic zebrafish xenograft model (eZXM) to visualize and track metastatic cells in real time using selective plane illumination microscopy (SPIM) for up to 30 h. Injected human leukemic and breast cancer cells exhibited cell-type specific patterns of intravascular distribution with leukemic cells moving faster than breast cancer cells.

Author Correction: Defined Geldrop Cultures Maintain Neural Precursor Cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Multiphasic microgel-in-gel materials to recapitulate cellular mesoenvironments in vitro.

Multiphasic in vitro models with cross-scale heterogeneity in matrix properties and/or cellular composition can reflect the structural and compositional complexity of living tissues more faithfully, thereby creating new options for pathobiology and drug development studies. Herein, a new class of tunable microgel-in-gel materials is reported that build on a versatile platform of multifunctional poly(ethylene glycol)-heparin gel types and integrates monodisperse, cell-laden microgels within cell-laden bulk hydrogel matrices. A novel microfluidic approach was developed to enable the high-throughput fabrication of microgels of in situ adjustable diameters, stiffness, degradability and biomolecular functionalization.

Defined Geldrop Cultures Maintain Neural Precursor Cells.

Distinct micro-environmental properties have been reported to be essential for maintenance of neural precursor cells (NPCs) within the adult brain. Due to high complexity and technical limitations, the natural niche can barely be studied systematically in vivo. By reconstituting selected environmental properties (adhesiveness, proteolytic degradability, and elasticity) in geldrop cultures, we show that NPCs can be maintained stably at high density over an extended period of time (up to 8 days).

Lysophosphatidic Acid Receptor Is a Functional Marker of Adult Hippocampal Precursor Cells.

Here, we show that the lysophosphatidic acid receptor 1 (LPA1) is expressed by a defined population of type 1 stem cells and type 2a precursor cells in the adult mouse dentate gyrus. LPA1, in contrast to Nestin, also marks the quiescent stem cell population. Combining LPA1-GFP with EGFR and prominin-1 expression, we have enabled the prospective separation of both proliferative and non-proliferative precursor cell populations.

A co-culture model of the hippocampal neurogenic niche reveals differential effects of astrocytes, endothelial cells and pericytes on proliferation and differentiation of adult murine precursor cells.

The niche concept of stem cell biology proposes a functional unit between the precursor cells and their local microenvironment, to which several cell types might contribute by cell-cell contacts, extracellular matrix, and humoral factors. We here established three co-culture models (with cell types separated by membrane) for both adherent monolayers and neurospheres to address the potential influence of different niche cell types in the neurogenic zone of the adult hippocampus of mice. Astrocytes and endothelial cells enhanced precursor cell proliferation and neurosphere formation.

Extracellular matrix deposition of bone marrow stroma enhanced by macromolecular crowding.

Decellularized extracellular matrices (ECM) from in vitro cell cultures can serve as in vivo-like matrix scaffolds for modulating cell-ECM interactions. Macromolecular crowding (MMC), the supplementation of synthetic or naturally occurring molecules resulting in excluded volume effects (EVE), has been demonstrated to provide valuable options for recapitulating the physiological environment of cells during matrix secretion. Human mesenchymal stem cell (MSC)-derived ECM was produced upon supplementation of standard culture medium with three different macromolecules of various size (10-500 kDa).

Mouse model of CADASIL reveals novel insights into Notch3 function in adult hippocampal neurogenesis.

Could impaired adult hippocampal neurogenesis be a relevant mechanism underlying CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy)? Memory symptoms in CADASIL, the most common hereditary form of vascular dementia, are usually thought to be primarily due to vascular degeneration and white matter lacunes. Since adult hippocampal neurogenesis, a process essential for the integration of new spatial memory occurs in a highly vascularized niche, we considered dysregulation of adult neurogenesis as a potential mechanism for the manifestation of dementia in CADASIL. Analysis in aged mice overexpressing Notch3 with a CADASIL mutation, revealed vascular deficits in arteries of the hippocampal fissure but not in the niche of the dentate gyrus.

Thermoswitching microgel carriers improve neuronal cell growth and cell release for cell transplantation.

Successful cell replacement therapy in the central nervous system (CNS) depends on both the transplanted cell type and the cell delivery method. It was established that differentiated neurons are the most desirable cell source; however, they are highly sensitive to dissociation shear; removing them from the growth surface inflicts serious damage, rendering them less viable for transplantation. Pilot experiments using glass colloids as injectable cell carriers for cell transplantation in the adult rat hippocampus have greatly improved neuron survival and long-term neuron integration.

Cryogel micromechanics unraveled by atomic force microscopy-based nanoindentation.

Cell-instructive physical characteristics of macroporous scaffolds, developed for tissue engineering applications, often remain difficult to assess. Here, an atomic force microscopy-based nanoindentation approach is adapted to quantify the local mechanical properties of biohybrid glycosaminoglycan-poly(ethylene glycol) cryogels. Resulting from cryoconcentration effects upon gel formation, cryogel struts are observed to feature a higher stiffness compared to the corresponding bulk hydrogel materials.