In the bone marrow (BM), hematopoietic stem cells (HSCs) lodge in specialized microenvironments that tightly control their proliferative state to adapt to the varying needs for replenishment of blood cells while also preventing exhaustion1. All putative niche cells suggested thus far have a non-hematopoietic origin2-8. Thus, it remains unclear how feedback from mature cells is conveyed to HSCs to adjust proliferation. Here we show that megakaryocytes (Mk) can directly regulate HSC pool size. Three-dimensional whole-mount imaging revealed that endogenous HSCs are frequently located adjacent to Mk in a non-random fashion. Selective in vivo depletion of Mk resulted in specific loss of HSC quiescence and led to a marked expansion of functional HSCs. Gene expression analyses revealed that Mk were the source of chemokine C-X-C motif ligand 4 (Cxcl4, also named platelet factor 4, Pf4) in the BM and Cxcl4 injection reduced HSC numbers via increased quiescence. By contrast, Cxcl4−/− mice exhibited increased HSC numbers and proliferation. Combined use of whole-mount imaging and computational modelling was highly suggestive of a megakaryocytic niche capable of influencing independently HSC maintenance by regulating quiescence. Thus, these results indicate that a terminally differentiated HSC progeny contributes to niche activity by directly regulating HSC behavior.

We were able to define predictors of admission for patients having LH/RAH managed with an ERAS pathway. Increased ASA physical status, being African American, and increased length of procedure were significantly associated with admission after LH/RAH performed under an ERAS pathway. In addition, the incidences of urgent clinic and ER visits, readmissions, and reoperations within 90 days of surgery were similar for patients who were discharged on the day of surgery compared to those admitted.

Epithelial to mesenchymal transition (EMT) is a biological process involved in tissue morphogenesis and disease that causes dramatic changes in cell morphology, migration, proliferation, and gene expression. The retinal pigment epithelium (RPE), which supports the neural retina, can undergo EMT, producing fibrous epiretinal membranes (ERMs) associated with vision-impairing clinical conditions, such as macular pucker and proliferative vitreoretinopathy (PVR). We found that co-treatment with TGF-b and TNF-a (TNT) accelerates EMT in adult human RPE stem cell-derived RPE cell cultures. We captured the global epigenomic and transcriptional changes elicited by TNT treatment of RPE and identified putative active enhancers associated with actively transcribed genes, including a set of upregulated transcription factors that are candidate regulators. We found that the vitamin B derivative nicotinamide downregulates these key transcriptional changes, and inhibits and partially reverses RPE EMT, revealing potential therapeutic routes to benefit patients with ERM, macular pucker and PVR.

Background and Objectives:Robotic surgery has introduced unique challenges to surgical workflow. The association between quality of communication in robotic-assisted laparoscopic surgery and surgical outcomes was evaluated.Methods:After each gynecologic robotic surgery, the team members involved in the surgery completed a survey regarding the quality of communication. A composite quality-of-communication score was developed using principal component analysis. A higher composite quality-of-communication score signified poor communication.Objective parameters, such as operative time and estimated blood loss (EBL), were gathered from the patient's medical record and correlated with the composite quality-of-communication scores.Results:Forty robotic cases from March through May 2013 were included. Thirty-two participants including surgeons, circulating nurses, and surgical technicians participated in the study. A higher composite quality-of-communication score was associated with greater EBL (P = .010) and longer operative time (P = .045), after adjustment for body mass index, prior major abdominal surgery, and uterine weight. Specifically, for every 1-SD increase in the perceived lack of communication, there was an additional 51 mL EBL and a 31-min increase in operative time. The most common reasons reported for poor communication in the operating room were noise level (28/36, 78%) and console-to-bedside communication problems (23/36, 64%).Conclusion:Our study demonstrates a significant association between poor intraoperative team communication and worse surgical outcomes in robotic gynecologic surgery. Employing strategies to decrease extraneous room noise, improve console-to-bedside communication and team training may have a positive impact on communication and related surgical outcomes.

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Drug discovery for diseases such as Parkinson’s disease are impeded by the lack of screenable cellular phenotypes. We present an unbiased phenotypic profiling platform that combines automated cell culture, high-content imaging, Cell Painting, and deep learning. We applied this platform to primary fibroblasts from 91 Parkinson’s disease patients and matched healthy controls, creating the largest publicly available Cell Painting image dataset to date at 48 terabytes. We use fixed weights from a convolutional deep neural network trained on ImageNet to generate deep embeddings from each image and train machine learning models to detect morphological disease phenotypes. Our platform’s robustness and sensitivity allow the detection of individual-specific variation with high fidelity across batches and plate layouts. Lastly, our models confidently separate LRRK2 and sporadic Parkinson’s disease lines from healthy controls (receiver operating characteristic area under curve 0.79 (0.08 standard deviation)), supporting the capacity of this platform for complex disease modeling and drug screening applications.

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