Collective cell migration is an adaptive, coordinated interactive process involving cell-cell and cell-extracellular matrix (ECM) microenvironmental interactions. A critical aspect of collective migration is the sensing and establishment of directional movement. It has been proposed that a subgroup of cells known as leader cells localize at the front edge of a collectively migrating cluster and are responsible for directing migration. However, it is unknown how and when leader cells arrive at the front edge and what environmental cues dictate leader cell development and behavior. Here, we addressed these questions by combining a microfluidic device design that mimics multiple tumor microenvironmental cues concurrently with biologically relevant primary, heterogeneous tumor cell organoids. Prior to migration, breast tumor leader cells (K14 þ) were present throughout a tumor organoid and migrated (polarized) to the leading edge in response to biochemical and biomechanical cues. Impairment of either CXCR4 (biochemical responsive) or the collagen receptor DDR2 (biomechanical responsive) abrogated polarization of leader cells and directed collective migration. This work demonstrates that K14 þ leader cells utilize both chemical and mechanical cues from the microenvironment to polarize to the leading edge of collectively migrating tumors. Significance: These findings demonstrate that pre-existing, randomly distributed leader cells within primary tumor organoids use CXCR4 and DDR2 to polarize to the leading edge and direct migration.

The theory of natural selection has been vital in unifying the biological sciences and their research with a single testable metatheory. Despite a plethora of research supporting natural selection, teaching the theory of evolution remains controversial in high schools and higher education (Wilson et al. 2009;Scott 1997). In this article, we sample the attitudes toward evolution of 170 faculty and graduate and undergraduate students in family studies and human development programs from across the United States to determine whether resistances toward evolution remain and to describe the correlates of these resistances. Results reveal that an individual's prosocial meliorist attitudes, religious ideation, and his or her reported interest in and knowledge of evolution all uniquely contribute to whether they report evolutionary theory as being applicable to their area of research interests. We discuss the relevance of including evolutionary theory within family studies and human development research programs and make suggestions for how to implement an evolutionary studies program (Wilson et al. 2009).

Background: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy has shown to improve survival in patients with extensive or refractory abdominal tumors of many different histologies. Postoperative pain control can be challenging as the surgical procedure is performed through a midline laparotomy incision from xiphoid to symphysis pubis, and patients are usually nothing by mouth for the first 8-10 postoperative days. Aims:We present the anesthetic management and postoperative pain control strategies for cytoreductive surgery with hyperthermic intraperitoneal chemotherapy using a multimodal, opioid-sparing, and total intravenous anesthetic technique with a tunneled thoracic epidural.Methods: A single institution retrospective review of anesthetic management, intraoperative fluid and blood administration, and postoperative pain control for pediatric patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy between July 2018 and December 2020 was conducted. We employed a novel anesthetic and analgesia protocol consisting of premedication with gabapentin followed by intraoperative infusions of propofol, dexmedetomidine, ketamine, and cisatracurium. A tunneled thoracic epidural catheter was placed for management of pain. Results:We reviewed and analyzed the first 25 patient records. The most common diagnosis was desmoplastic small round cell tumor (n = 12). Median age of patients was 14 years (range 21 months-22 years). All patients were extubated in the operating room and no patients required reintubation. There were no incidences of acute kidney injury. Epidural infusions were used for a median of 8 days (range 2-14 days). Median postoperative intravenous opioid use (morphine equivalent) through postoperative day 10 was 0.02 mg/kg/day (range 0-0.86 mg/kg/day) administered for a median of 2 days (range 0-17 days). Nine patients (36%) did not require any intravenous opioids in the postoperative period.Conclusions: Utilizing a multimodal, opioid-sparing, total intravenous anesthetic technique in conjunction with a tunneled thoracic epidural catheter, we were able to avoid the need for postoperative mechanical ventilation and minimize both intraoperative and postoperative opioid requirements.

In this study the author examined the developmental differences in inhibition and cognition of 4-8-year-old children as a function of the suggested presence of a supernatural agent. Previous evolutionarily-relevant research has suggested that humans are naturally primed to think in terms of supernatural agents and that, given the correct context, individuals readily accept novel supernatural entities and alter their behavior accordingly. All children in this study played 4 games designed to assess their present level of inhibitory and cognitive development. Children in the experimental condition were also introduced to an invisible Princess Alice and were told that she was watching during the games. Following these measures, all children engaged in a resistance-to-temptation task. Results revealed that cognitively advanced children were more likely to express belief in Princess Alice than were less cognitively advanced children. This research provides support that cognitive maturity, rather than immaturity, may be necessary for children to express belief in novel supernatural agents.

<p>These are the movie legends and supplemental methods</p>