CIC-DUX4 Sarcoma Involving the Skull Base: A Rare Presentation and Review of the Literature.

Background CIC-DUX4 sarcoma is a rare, aggressive tumor that is difficult to diagnose. Although it is closely related to Ewing's sarcoma, each is a distinct pathologic entity and both have been previously reported in the skin, lymph nodes, and viscera. We report the first description of CIC-DUX4 involving the posterior cranial fossa and review the distinctive symptomatology, morphology, immunoprofile, and genetic signature that differentiate this rare tumor. Case Report A 32-year-old man presented with an enlarging right lateral neck mass, progressive hoarseness, and orofacial pain. Biopsy revealed a high-grade undifferentiated malignant neoplasm. Imaging demonstrated an 8-cm mass in the right neck extending to the skull base and abutting the carotid sheath, in addition to pulmonary nodules and pelvic lymphadenopathy. Despite initial response to chemotherapy, he experienced disease progression and underwent surgical resection, radical neck dissection, and brachytherapy. Definitive pathologic diagnosis was achieved with next-generation sequencing. Within weeks of treatment, he developed symptoms reflecting progression of disease involving the neck, posterior cranial fossa, and lung. Adjuvant chemotherapy was planned, but the patient succumbed to his disease prior to initiation of further therapy. Conclusion CIC-DUX4 sarcomas are uncommon and can progress rapidly. Diagnosis requires either fluorescence in situ hybridization or next-generation sequencing. Due to its rarity, there is no standard-of-care treatment for this tumor and further investigations are needed to understand disease behavior and develop targeted therapeutic modalities.

Practical Scientific Writing and Publishing in Anatomic Pathology.

OBJECTIVES: To develop a structured, introductory curriculum in scientific writing and publishing for residents in anatomic pathology. METHODS: We assessed the need for this curriculum by using an online questionnaire sent to anatomic pathology residents in our program and tailored content to address areas of least familiarity. The curriculum consisted of 4 virtual lectures delivered by select experts in the field. Curriculum evaluation was assessed through a postcurriculum questionnaire. RESULTS: In total, 27 of 31 (87%) residents responded to the initial questionnaire. The major educational need was identified in the following topics: "responsibilities of a corresponding author"; "selecting a journal for publication"; "editor's approach to evaluating a manuscript"; "correspondence with editors and reviewers"; and "open access, cost and increasing exposure to manuscript." Eight residents participated in at least 3 of 4 lectures and completed the pre- and postcurriculum survey. The postcurriculum survey demonstrated statistically significant interval increases in familiarity with 7 of 18 topics, and the leading increases were noted in topics of most significant educational need. CONCLUSIONS: Development of novel curricula is vital to the ever-changing landscape of pathology resident education. This study proposes a generalizable algorithmic approach to assessing new areas of educational need and effectively addressing them through targeted curricula.

Pvr and distinct downstream signaling factors are required for hemocyte spreading and epidermal wound closure at Drosophila larval wound sites.

Tissue injury is typically accompanied by inflammation. In Drosophila melanogaster larvae, wound-induced inflammation involves adhesive capture of hemocytes at the wound surface followed by hemocyte spreading to assume a flat, lamellar morphology. The factors that mediate this cell spreading at the wound site are not known. Here, we discover a role for the platelet-derived growth factor/vascular endothelial growth factor-related receptor (Pvr) and its ligand, Pvf1, in blood cell spreading at the wound site. Pvr and Pvf1 are required for spreading in vivo and in an in vitro spreading assay where spreading can be directly induced by Pvf1 application or by constitutive Pvr activation. In an effort to identify factors that act downstream of Pvr, we performed a genetic screen in which select candidates were tested to determine if they could suppress the lethality of Pvr overexpression in the larval epidermis. Some of the suppressors identified are required for epidermal wound closure (WC), another Pvr-mediated wound response, some are required for hemocyte spreading in vitro, and some are required for both. One of the downstream factors, Mask, is also required for efficient wound-induced hemocyte spreading in vivo. Our data reveal that Pvr signaling is required for wound responses in hemocytes (cell spreading) and defines distinct downstream signaling factors that are required for either epidermal WC or hemocyte spreading.

MicroRNA miR-7 Regulates Secretion of Insulin-Like Peptides.

The insulin/insulin-like growth factor (IGF) pathway is essential for linking nutritional status to growth and metabolism. MicroRNAs (miRNAs) are short RNAs that are players in the regulation of this process. The miRNA miR-7 shows highly conserved expression in insulin-producing cells across the animal kingdom. However, its conserved functions in regulation of insulin-like peptides (ILPs) remain unknown. Using Drosophila as a model, we demonstrate that miR-7 limits ILP availability by inhibiting its production and secretion. Increasing miR-7 alters body growth and metabolism in an ILP-dependent manner, elevating circulating sugars and total body triglycerides, while decreasing animal growth. These effects are not due to direct targeting of ILP mRNA, but instead arise through alternate targets that affect the function of ILP-producing cells. The Drosophila F-actin capping protein alpha (CPA) is a direct target of miR-7, and knockdown of CPA in insulin-producing cells phenocopies the effects of miR-7 on ILP secretion. This regulation of CPA is conserved in mammals, with the mouse ortholog Capza1 also targeted by miR-7 in ß-islet cells. Taken together, these results support a role for miR-7 regulation of an actin capping protein in insulin regulation, and highlight a conserved mechanism of action for an evolutionarily ancient microRNA.

Breathing Life into Shapes.

Shape articulation transforms a lifeless geometric object into a vibrant character. Computers enrich artists' toolsets dramatically. They not only endow artists with the power to manipulate virtual 2D and 3D scenes, but they also eliminate tedium and expedite prototyping, freeing artists to focus on creative aspects. With such power comes a temptation to lean entirely on the computer. Computationally intensive animation systems sacrifice real-time feedback for physical accuracy. How can we leverage modern computational power to create the best possible shape deformations while maintaining real-time performance as a mandatory invariant? This article summarizes efforts to answer this, culminating in a deformation system with the quality of slow, nonlinear optimization, but at lightning speed.

Fast and Memory-Efficient Topological Denoising of 2D and 3D Scalar Fields.

Data acquisition, numerical inaccuracies, and sampling often introduce noise in measurements and simulations. Removing this noise is often necessary for efficient analysis and visualization of this data, yet many denoising techniques change the minima and maxima of a scalar field. For example, the extrema can appear or disappear, spatially move, and change their value. This can lead to wrong interpretations of the data, e.g., when the maximum temperature over an area is falsely reported being a few degrees cooler because the denoising method is unaware of these features. Recently, a topological denoising technique based on a global energy optimization was proposed, which allows the topology-controlled denoising of 2D scalar fields. While this method preserves the minima and maxima, it is constrained by the size of the data. We extend this work to large 2D data and medium-sized 3D data by introducing a novel domain decomposition approach. It allows processing small patches of the domain independently while still avoiding the introduction of new critical points. Furthermore, we propose an iterative refinement of the solution, which decreases the optimization energy compared to the previous approach and therefore gives smoother results that are closer to the input. We illustrate our technique on synthetic and real-world 2D and 3D data sets that highlight potential applications.