Deep learning predicts function of live retinal pigment epithelium from quantitative microscopy.

Increases in the number of cell therapies in the preclinical and clinical phases have prompted the need for reliable and non-invasive assays to validate transplant function in clinical biomanufacturing. We developed a robust characterization methodology composed of quantitative bright-field absorbance microscopy (QBAM) and deep neural networks (DNNs) to non-invasively predict tissue function and cellular donor identity. The methodology was validated using clinical-grade induced pluripotent stem cell derived retinal pigment epithelial cells (iPSC-RPE). QBAM images of iPSC-RPE were used to train DNNs that predicted iPSC-RPE monolayer transepithelial resistance, predicted polarized vascular endothelial growth factor (VEGF) secretion, and matched iPSC-RPE monolayers to the stem cell donors. DNN predictions were supplemented with traditional machine learning algorithms that identified shape and texture features of single cells that were used to predict tissue function and iPSC donor identity. These results demonstrate non-invasive cell therapy characterization can be achieved with QBAM and machine learning

Selective angioembolization for traumatic renal injuries: a survey on clinician practice

PURPOSE: A variety of clinical and imaging findings are used by clinicians to determine utility of renal angioembolization (AE) in managing renal trauma. Our purpose was to investigate specific criteria that clinicians who manage high-grade renal trauma (HGRT) utilize in decision-making for primary or delayed AE. METHODS: A total of 413 urologists and interventional radiologists (IRs) who practice at level 1 or 2 trauma centers within the United States were provided an original survey via email on experience and opinions regarding the utility of AE for HGRT. We described overall practice patterns and assessed differences by clinician type, using the Fisher’s exact test. RESULTS: A total of 79 (20 %) clinicians completed the survey. All clinicians had AE capability for HGRT management. A higher proportion of IRs reported using AE for grade I–II (33 vs. 3 %, p = 0.002), grade III (65 vs. 26 %, p = 0.001), and penetrating injuries (83 vs. 58 %, p = 0.02). A greater proportion of urologists reported using AE for grade V injuries (81 vs. 56 %, p = 0.03). Clinicians most commonly cited computed tomography evidence of active arterial bleeding (97 %), or arteriovenous fistula/pseudoaneurysm (94 %) as indications for primary AE, and 62 % identified concurrent visceral injury as factor that would necessitate surgical intervention. CONCLUSION: In a survey of clinicians, we report that IRs and urologists utilize AE differently when managing HGRT, as a higher proportion of IRs use AE to manage lower grade as well as penetrating injuries. Validation studies are needed to establish algorithms to identify patients with HGRT who would benefit from selective renal AE

The molecular architecture of lamins in somatic cells

The nuclear lamina is a fundamental constituent of metazoan nuclei. It is composed mainly of lamins, which are intermediate filament proteins that assemble into a filamentous meshwork, bridging the nuclear envelope and chromatin. Besides providing structural stability to the nucleus, the lamina is involved in many nuclear activities, including chromatin organization, transcription and replication. However, the structural organization of the nuclear lamina is poorly understood. Here we use cryo-electron tomography to obtain a detailed view of the organization of the lamin meshwork within the lamina. Data analysis of individual lamin filaments resolves a globular-decorated fibre appearance and shows that A- and B-type lamins assemble into tetrameric filaments of 3.5 nm thickness. Thus, lamins exhibit a structure that is remarkably different from the other canonical cytoskeletal elements. Our findings define the architecture of the nuclear lamin meshworks at molecular resolution, providing insights into their role in scaffolding the nuclear lamina