Targeting PIM2 by JP11646 results in significant antitumor effects in solid tumors.

Proviral integration of Moloney virus 2 (PIM2) is a pro­survival factor of cancer cells and a possible therapeutic target in hematological malignancies. However, the attempts at inhibiting PIM2 have yielded underwhelming results in early clinical trials on hematological malignancies. Recently, a novel pan­PIM inhibitor, JP11646, was developed. The present study examined the utility of targeting PIM2 in multiple solid cancers and investigated the antitumor efficacy and the mechanisms of action of JP11646. When PIM2 expression was compared between normal and cancer tissues in publicly available datasets, PIM2 was found to be overexpressed in several types of solid cancers. PIM2 ectopic overexpression promoted tumor growth in in vivo xenograft breast cancer mouse models. The pan­PIM inhibitor, JP11646, suppressed in vitro cancer cell proliferation in a concentration­dependent manner in multiple types of cancers; a similar result was observed with siRNA­mediated PIM2 knockdown, as well as an increased in cell apoptosis. By contrast, another pan­PIM inhibitor, AZD1208, suppressed the expression of downstream PIM2 targets, but not PIM2 protein expression, corresponding to no apoptosis induction. As a mechanism of PIM2 protein degradation, it was found that the proteasome inhibitor, bortezomib, reversed the apoptosis induced by JP11646, suggesting that PIM2 degradation by JP11646 is proteasome­dependent. JP11646 exhibited significant anticancer efficacy with minimal toxicities at the examined doses and schedules in multiple in vivo mice xenograft solid cancer models. On the whole, the present study demonstrates that PIM2 promotes cancer progression in solid tumors. JP11646 induces apoptosis at least partly by PIM2 protein degradation and suppresses cancer cell proliferation in vitro and in vivo. JP11646 may thus be a possible treatment strategy for multiple types of solid cancers.

Wooded Semi-Natural Habitats Complement Permanent Grasslands in Supporting Wild Bee Diversity in Agricultural Landscapes.

Loss of semi-natural habitats (SNH) in agricultural landscapes affects wild bees, often negatively. However, how bee communities respond varies and is still unclear. To date, few studies have used precise descriptors to understand these effects. Our aim was to understand the respective and complementary influences of different wooded and herbaceous habitats on wild bee communities. We selected thirty 500-m radius landscapes on a gradient of a percentage of wooded SNH in south-western France. At each landscape, we sampled wild bees in spring 2016 and plants in spring 2015 and 2016 at the forest edge, in a hedgerow, and in a permanent grassland. Pollen carried by the most abundant bee species was collected and identified. Using beta diversity indices, we showed that wild bee community composition differs between the three SNH types, and especially between herbaceous and wooded SNH. Based on Jacobs' selection index, we showed that pollen of some plant species recorded in wooded SNH are preferentially selected by wild bees. Studying the impact of the loss of each SNH type on the global bee-pollen interaction network, we found that wooded SNH contributed to its resilience, enabling specific plant-bee interactions. Overall, our results underline the non-negligible contribution of wooded SNH to the diversity of wild bees in agricultural landscapes, and thus the importance of maintaining different types of SNH.

Developing and testing a comprehensive tool to assess family meetings: Empirical distinctions between high- and low-quality meetings.

BACKGROUND: The heterogeneity with regard to findings on family meetings (or conferences) suggests a need to better understand factors that influence family meetings. While earlier studies have explored frequency or timing of family meetings, little is known about how factors (such as what is said during meetings, how it is said, and by whom) influence family meeting quality. OBJECTIVES: (1) To develop an evaluation tool to assess family meetings (Phase 1); (2) to identify factors that influence meeting quality by evaluating 34 family meetings (Phase 2). MATERIALS AND METHODS: For Phase 1, methods included developing a framework, cognitive testing, and finalizing the evaluation tool. The tool consisted of Facilitator Characteristics (i.e., gender, experience, and specialty of the person leading the meeting), and 22 items across 6 Meeting Elements (i.e., Introductions, Information Exchanges, Decisions, Closings, Communication Styles, and Emotional Support) and sub-elements. For Phase 2, methods included training evaluators, assessing family meetings, and analyzing data. We used Spearman's rank-order correlations to calculate meeting quality. Qualitative techniques were used to analyze free-text. RESULTS: No Facilitator Characteristic had a significant correlation with meeting quality. Sub-elements related to communication style and emotional support most strongly correlated with high-quality family meetings, as well as whether "next steps" were outlined (89.66%) and whether "family understanding" was elicited (86.21%). We also found a significant and strong positive association between overall proportion scores and evaluators' ratings (rs=0.731, p<0.001). CONCLUSIONS: We filled a gap by developing an evaluation tool to assess family meetings, and we identified how what is said during meetings impacts quality.