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This report describes a patient with metastatic epithelioid hemangioendothelioma treated with bevacizumab and nanoparticle albumin-bound paclitaxel. The treatment was well tolerated and led to the stabilization of an aggressive variant of the disease. This case report is the first one that describes the activity of the combination of chemotherapy and bevacizumab in epithelioid hemangioendothelioma. Literature describing the activity of bevacizumab and other agents (thalidomide, lenalidomide, and interferon) believed to possess anti-angiogenic activities is also reviewed. [ABSTRACT FROM AUTHOR]

A 60 year old male had an open thoracotomy for bronchogenic carcinoma. On the twelfth hospital day he became obtunded and complained of headache. Radiographs revealed intracranial air. It was thought that the pneumocephalus in this patient was most likely secondary to a tension pneumothorax continuously forcing air through a dural tear sustained at the time of initial surgery. The causes of pneumocephalus are reviewed and no similar case report has been found in the literature. [ABSTRACT FROM AUTHOR]

Although CRISPR-Cas9 genome editing can be performed directly in single-cell mouse zygotes, the targeting efficiency for more complex modifications such as the insertion of two loxP sites, multiple mutations in cis, or the precise insertion or deletion of longer DNA sequences often remains low (Cohen, 2016). Thus, targeting and validation of correct genomic modification in murine embryonic stem cells (ESCs) with subsequent injection into early-stage mouse embryos may still be preferable, allowing for large-scale screening in vitro before transfer of thoroughly characterized and genetically defined ESC clones into the germline. This procedure can result in a reduction of animal numbers with cost effectiveness and compliance with the 3R principle of animal welfare regulations. Here, we demonstrate that after transfection of homology templates and PX458 CRISPR-Cas9 plasmids, EGFP-positive ESCs can be sorted with a flow cytometer for the enrichment of CRISPR-Cas9-expressing cells. Cell sorting obviates antibiotic selection and therefore allows for more gentle culture conditions and faster outgrowth of ESC clones, which are then screened by qPCR for correct genomic modifications. qPCR screening is more convenient and less time-consuming compared to analyzing PCR samples on agarose gels. Positive ESC clones are validated by PCR analysis and sequencing and can serve for injection into early-stage mouse embryos for the generation of chimeric mice with germline transmission. Therefore, we describe here a simple and straightforward protocol for CRISPR-Cas9-directed gene targeting in ESCs. Graphical abstract., (Copyright © 2022 The Authors; exclusive licensee Bio-protocol LLC.)

Balanced control of T cell signaling is critical for adaptive immunity and protection from autoimmunity. By combining genetically engineered mouse models, biochemical analyses and pharmacological interventions, we describe an unexpected dual role of the tumor necrosis factor receptor–associated factor 6 (TRAF6) E3 ligase as both a positive and negative regulator of mucosa-associated lymphoid tissue 1 (MALT1) paracaspase. Although MALT1-TRAF6 recruitment is indispensable for nuclear factor κB signaling in activated T cells, TRAF6 counteracts basal MALT1 protease activity in resting T cells. In mice, loss of TRAF6-mediated homeostatic suppression of MALT1 protease leads to severe autoimmune inflammation, which is completely reverted by genetic or therapeutic inactivation of MALT1 protease function. Thus, TRAF6 functions as a molecular brake for MALT1 protease in resting T cells and a signaling accelerator for MALT1 scaffolding in activated T cells, revealing that TRAF6 controls T cell activation in a switch-like manner. Our findings have important implications for development and treatment of autoimmune diseases.

Purpose: To determine how to optimize the delivery of machine learning techniques in a clinical setting to detect intracranial hemorrhage (ICH) on non-contrast-enhanced CT images to radiologists to improve workflow., Materials and Methods: In this study, a commercially available machine learning algorithm that flags abnormal noncontrast CT examinations for ICH was implemented in a busy academic neuroradiology practice between September 2017 and March 2019. The algorithm was introduced in three phases: (a) as a "pop-up" widget on ancillary monitors, (b) as a marked examination in reading worklists, and (c) as a marked examination for reprioritization based on the presence of the flag. A statistical approach, which was based on a queuing theory, was implemented to assess the impact of each intervention on queue-adjusted wait and turnaround time compared with historical controls., Results: Notification with a widget or flagging the examination had no effect on queue-adjusted image wait ( P > .99) or turnaround time ( P = .6). However, a reduction in queue-adjusted wait time was observed between negative (15.45 minutes; 95% CI: 15.07, 15.38) and positive (12.02 minutes; 95% CI: 11.06, 12.97; P < .0001) artificial intelligence-detected ICH examinations with reprioritization. Reduced wait time was present for all order classes but was greatest for examinations ordered as routine for both inpatients and outpatients because of their low priority., Conclusion: The approach used to present flags from artificial intelligence and machine learning algorithms to the radiologist can reduce image wait time and turnaround times.© RSNA, 2021See also the commentary by O'Connor and Bhalla in this issue., Competing Interests: Disclosures of Conflicts of Interest: T.J.O. disclosed no relevant relationships. Y.X. disclosed no relevant relationships. E.S. disclosed no relevant relationships. T.B. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: consultant to Change Healthcare. Other relationships: disclosed no relevant relationships. Y.N. disclosed no relevant relationships. C.B. disclosed no relevant relationships. R.P. disclosed no relevant relationships., (2021 by the Radiological Society of North America, Inc.)

Bone marrow-derived cells (BMCs) have been implicated as a modifiers of vascular growth either directly by transdifferentiation into endothelial cells (ECs) or indirectly through growth factor release. To examine these possibilities under physiological conditions, we developed a model of hypoxia-mediated angiogenesis in the mouse spinotrapezius muscle. This allows whole-mount analysis; therefore, the morphology and location of BMCs within the vascular network may be observed along with differentiation markers. We exposed bone marrow transplant chimeric mice to hypoxia and treated a subset with granulocyte macrophage colony-stimulating factor. Exposure to hypoxia caused an 13% increase in capillary density relative to control. Hypoxia did not increase the overall number of muscle-resident BMCs, but did increase the number of rounded BMCs by 25%. There was no discernable BMC contribution to the endothelium, although some BMCs assumed a pericyte morphology around capillaries. Granulocyte macrophage colony-stimulating factor treatment further increased the number of round BMCs within the muscle and caused a 23% increase in angiogenesis. The results of this study suggest a potentially beneficial action of BMCs during hypoxia through paracrine release of growth factors but not transdifferentiation into ECs.