Inhibition of SDF-1-induced migration of oncogene-driven myeloid leukemia by the L-RNA aptamer (Spiegelmer), NOX-A12, and potentiation of tyrosine kinase inhibition

Resistance to targeted tyrosine kinase inhibitors (TKI) remains a challenge for the treatment of myeloid leukemias. Following treatment with TKIs, the bone marrow microenvironment has been found to harbor a small pool of surviving leukemic CD34+ progenitor cells. The long-term survival of these leukemic cells has been attributed, at least in part, to the protective effects of bone marrow stroma. We found that the NOX-A12 'Spiegelmer', an L-enantiomeric RNA oligonucleotide that inhibits SDF-1α, showed in vitro and in vivo activity against BCR-ABL- and FLT3-ITD-dependent leukemia cells. NOX-A12 was sufficient to suppress SDF-1-induced migration in vitro. The combination of NOX-A12 with TKIs reduced cell migration in the same in vitro model of SDF-1-induced chemotaxis to a greater extent than either drug alone, suggesting positive cooperativity as a result of the SDF-1 blocking function of NOX-A12 and cytotoxicity resulting from targeted oncogenic kinase inhibition. These results are consistent with our in vivo findings using a functional pre-clinical mouse model of chronic myeloid leukemia (CML), whereby we demonstrated the ability of NOX-A12, combined with the ABL kinase inhibitor, nilotinib, to reduce the leukemia burden in mice to a greater extent than either agent alone. Overall, the data support the idea of using SDF-1 inhibition in combination with targeted kinase inhibition to override drug resistance in oncogene-driven leukemia to significantly diminish or eradicate residual leukemic disease

Populism in context. A cross-country investigation of the Facebook usage of populist appeals during the 2019 European Parliament elections

By providing populist movements with a suitable platform to invoke the support of ordinary people against the establishment, research has found that social media has facilitated the rise of populism in many Western democracies (Gerbaudo, 2018). Significant scholarly attention has recently been paid to how populist rhetoric is adopted by politicians in various (non)electoral contexts (Jagers & Walgrave, 2007; Bos & Brants, 2014; Ernst et al., 2019) and how such rhetoric diffuses through public discourse (Mazzoleni & Bracciale, 2018). However, while much existing scholarship has primarily focused on the prevalence of populist communication in political discourse (Reinemann et al., 2016; Ernst et al., 2019), less attention has been paid to the overall context of its use. This is an important shortcoming because if populist communication is a strategic tool (Weyland, 2001), it is important to uncover the conditions under which it is more or less likely to appear. In this paper we focus on these conditions through a more granular analysis of the use of populist appeals. First, at the (social media) post-level, we examine whether variations in content (topics and political level) are related to the use of populist appeals. Further, we bring attention to the relationship between populist appeals and party-level ideological leaning. We do this analysis within the context of the 2019 European Parliamentary (EP) elections, applying a quantitative content analysis of 8,074 Facebook posts from political parties representing twelve states and from across the ideological spectrum

A role for gut-associated lymphoid tissue in shaping the human B cell repertoire

PMCID: PMC3754866Rockefeller University Press grants the public the non-exclusive right to copy, distribute, or display this Work under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/ and http://creativecommons.org/licenses/by-nc-sa/3.0/legalcode

Patterns of negative campaigning during the 2019 European election: Political parties’ Facebook posts and users’ sharing behaviour across twelve countries

Focusing on the 2019 European Parliament campaign, we investigate parties’ engagement in negative campaigning on Facebook and the relationship to a parties’ ideology and their status as governing versus opposition party at the national level. Manual coding of 8,153 Facebook posts of parties from twelve European countries shows parties create less negative posts than positive and neutral ones. However, these negative posts attract more shares than positive, neutral, and balanced statements, which increases their prominence on the platform. Hence, users and algorithms create a negative campaign environment on Facebook to a greater extent than parties

The Polyphonic Sounds of Europe: Users’ Engagement With Parties’ European‐Focused Facebook Posts

It is an old concern in public and academic debates that people are not interested in European‐level issues, and even European Parliamentary election campaigns, which are the main democratic tools of the European Union (EU) to involve ordinary people into political decision‐making, are mostly about national‐level political topics. Moreover, even when European issues emerge, the context of its discussion is often harmful to European integration and strengthens the per‐ ceived importance of domestic politics. In the age of social media, however, users’ content preferences may significantly affect the presence of different political levels in political campaigns, but these preferences are still largely uncovered in academic literature. To fill this gap, we investigate the direct and moderated effects of European‐focused Facebook posts on user engagement drawing upon a content analysis dataset including 9,688 posts of 68 parties from 12 EU countries. In line with the well‐known second‐order election hypothesis (Reif & Schmitt, 1980) we hypothesize a negative direct main effect. However, we also assume that this effect is moderated by several content‐, and party‐level factors, and when people engage with European‐level contents they do it with those ones that are posted by populist parties, focused on a few divisive hot topics, and are framed with a negative tone. Moreover, we expect cross‐country differences. We find that on the whole, user engagement with national‐level political content prevails over the European‐level, but in some countries there are no remarkable differences in user engagement patterns of the two levels. While our findings mostly confirm the second‐order election hypothesis, they also demonstrate that European politics can spread within social media platforms in a less divisive and negative way than we expected. European‐focused posts do not perform better when they are posted by populist parties, focused selectively on the salient issues of immigration or environment, or framed in a negative way

Gasless laparoscopy for benign gynecological diseases using an abdominal wall-lifting system

Objectives: The use of gasless laparoscopy with an abdominal wall-lifting device for benign gynecological diseases was compared to conventional laparoscopy with CO2 pneumoperitoneum. Methods: From February 2007 to July 2007, 76 women with uterine and/or adnexal benign diseases and candidates for laparoscopic surgery were recruited in this study. Thirty-two women underwent gasless laparoscopic surgery and 44 women underwent pneumoperitoneum laparoscopic surgery. Results: Diverse pathologies, including adnexal cyst, uterine myoma and ectopic pregnancy, were treated successfully with gasless laparoscopic surgery. Compared with the patients in the pneumoperitoneum group, the similar hospital stay (P=0.353) and intraoperative blood loss (P=0.157) were observed. However, the mean operative time in the gasless group was significantly longer than that in the pneumoperitoneum group (P=0.003). No severe intraoperative or postoperative complications were found in either group, except for one case of laparotomic conversion in the pneumoperitoneum group due to dense pelvic adhesions. The total hospital charges were significantly less in the gasless group than in the pneumoperitoneum group (P=0.001). In 38 cases of ovarian cyst resection, the mean operative time in the gasless group remained longer than that in the pneumoperitoneum group (P=0.017). The total hospital charges were also significantly less in the gasless group than in the pneumoperitoneum group (P<0.001). Conclusion: Our preliminary results demonstrated that the laparoscopic procedure using the gasless technique was a safe, effective method to treat benign gynecological diseases. Moreover, it was easy to master. As a minimally invasive treatment, gasless laparoscopic surgery provides a good choice to patients in the undeveloped regions in China without increasing the patients’ and the government’s burden significantly