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

Divisive, negative, and populist?! An empirical analysis of European populist and mainstream parties’ use of digital political advertisements

For digital political advertising (DPA) on Facebook, parties can complement their organic communication by targeting users with sponsored posts (Facebook-sponsored posts) and advertising campaigns (Facebook ads). Based on the theoretical framework of dissonant public spheres in the digital age, this article provides the first empirical analysis of how and with what content populist and mainstream parties use DPA on Facebook for divisive, negative, and populist messages. We analyze a data set of approximately 10,000 Facebook organic posts, sponsored posts, and ads published by 53 parties across 10 European countries during the 2019 European parliamentary election. Our findings reveal that populist and mainstream parties do not sponsor more posts or spend more money on ads containing divisive topics, negativity, and populist communication styles. Our article extends the debate on digital public spheres by incorporating parties’ use of division, negativity, and populism in DPA, thus offering a better understanding of their implications for shaping dissonant public spheres

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

Gasless balloon laparoscopy

The concept of balloon laparoscopy (B-LSC) pursues the simplification of conventional diagnostic laparoscopy (LSC). The pneumoperitoneum is replaced by a transparent balloon, which is positioned in front of the optical system. It shall be shown that with this arrangement diagnostic LSC can be performed outside of the operating room without requiring general anesthesia.An inflatable balloon was developed for a 30°/3.5-mm rod lens. Intra-abdominally the balloon was expanded to a diameter of 30 mm by air insufflation, and B-LSC was performed. Twelve patients were examined in general anesthesia before laparoscopic surgery. Twelve patients were subjected to B-LSC fully awake or with sedation (midazolam or propofol/S-ketamine) as a “second-look” procedure by way of a flexible trocar (port) left in the abdominal wall at the end of previous operation. Eight patients have been first provided with a trocar under sedation (midazolam or propofol/S-ketamine) combined with local anesthesia, and B-LSC was performed before laparoscopic surgery.On a scale of 1–5, the general impression was rated 1.9, the navigability to the different abdominal organs 2.5, the resolution 1.5, the stability of the system optic/trocar 2.1, the suitability of the balloon format 1.9, and the stability of the balloon against lateral shear forces 2.4. The degree of painfulness of the examination was rated 2.8, the tolerance of the port 1.4, and the degree of painfulness of trocar placement at 2.5. On a scale of 1 to 3, the strain of the abdominal musculature was rated 1.4 and the obstruction by adhesions 1.7.B-LSC is technically practicable with good imaging qualities and without requiring pneumoperitoneum. It is tolerated in great extent under slight sedation and particularly well under deep sedation. The procedure is suitable for diagnostics of unclear abdominal conditions, as a second-look LSC and also as a staging LSC

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