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How do journalists think news avoidance can be addressed? We analyze how US journalists (N = 1,543) responded to two survey questions about consistent news avoidance: whether they believed it was possible to convert consistent news avoiders to news consumers (a closed-ended question) and, if so, how (an open-ended question). Two-thirds of respondents (66.3%) believed solutions were possible. Using the concept of boundary work to analyze their open-ended responses, we argue that by recommending solutions to news avoidance journalists rhetorically assert epistemic authority but also suggest scripts for future action to further defend it. Their most-often recommended solutions were that journalists increase relevance and positivity and expel bias and sensationalism—thereby defending some longstanding internal boundaries while redrawing others. We conclude that although these recommendations align well with reasons news avoiders say they avoid news, they often do not account for structural causes of news avoidance and face many barriers to implementation. [ABSTRACT FROM AUTHOR]

Scholars have long argued that incidental news exposure (INE) is a potentially valuable way citizens gain political information and learn about current affairs. Yet growing scholarship on news avoidance suggests many people still manage to consume little news, and algorithmic curation may decrease the likelihood that they will be exposed to it incidentally. In this article, we put the literatures on INE, news avoidance, and political talk into dialogue with one another. Then, by inductively analyzing over a hundred in-depth interviews conducted from 2016 to 2020 with news avoiders in the UK, Spain, and the United States, we explore how they encounter news incidentally and to what extent they feel the news is accessible and available to them. Our audience-centric approach highlights that interviewees often did not make a clear distinction between direct encounters with professional news ("firsthand news") and discussions of news ("secondhand news"), especially online. When they did make a distinction, the latter was often more salient for them. We also find that just as news consumers have repertoires of news sources on which they habitually rely, news avoiders have repertoires of sources for incidental exposure to news to stay informed about major events and anything that might affect them directly. And yet, those repertoires catch only the biggest and most sensational stories of the day and do little to help them contextualize or understand the news they encounter, contributing to their sense that news is neither entirely absent nor ambient in the way scholars have theorized. [ABSTRACT FROM AUTHOR]

Monkeypox is a reemerging zoonosis caused by Monkeypox virus (MPXV), a member of the genus Orthopoxvirus. MPXV is related to Variola virus, the causative agent of smallpox. Although infections with [...]

This article presents the results of an investigation into undergraduate students' perceptions of the influences of their mentored research experiences on their identity development. Data from a 2015 survey were analyzed using summative and inductive approaches. The results indicated that participants had access to multiple opportunities for mentored undergraduate research. Second, participants identified a constellation of mentor types that facilitated students' initial and long-term engagement in undergraduate research experiences. The inductive analysis of open-ended responses uncovered five categories of elements identified by participants as influencing their identity shifts and three domains of students' perceived identity shifts: disciplinary/professional, academic/researcher, and personal/cultural. The findings extend the literature related to outcomes of mentored undergraduate research and suggest a need for additional investigations into mentoring models that accommodate arrays of mentors and identity shifts associated with mentored undergraduate research.

The investigative setting for this study was an alternative educational program that serves at-risk middle and secondary school students. The study evaluated students' conceptual understandings of forgiveness, their exercise of forgiveness in the face of perceived school-related transgressions, as well as the relationship between the two variables and student mental health and well-being. Overall, the students' cognitive grasp of forgiveness was found to be less sophisticated than was demonstrated by a similar sample of adults, indicating that the students, as a group of externalizing youth, struggled to use forgiveness to resolve relational conflicts. Specific factors that may foster forgiveness in habitually aggressive youth are presented along with recommendations for interventions.

Objective: To assess the influence of F1174S mutation on kinase activity and drug sensitivity of the echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK) fusion (EML4-ALK) variants 1 and 3. Methods: We constructed mammalian expression plasmids of both wildtype and F1174 mutant EML4-ALK variants 1 and 3, and then characterized them with cell models by performing immunoblotting, neurite outgrowth assay, focus formation assay as well as protein stability assay. Drug sensitivity to ALK tyrosine kinase inhibitors was also compared between wildtype and F1174 mutant EML4-ALK fusions. In addition, we characterized the effect of different F1174 kinase domain mutations in the context of EML4-ALK fusions. Results: In contrast to the oncogenic ALK-F1174S mutation that has been reported to be activating in the context of full-length ALK in neuroblastoma, EML4-ALK (F1174S) variant 1 exhibits impaired kinase activity leading to loss of oncogenicity. Furthermore, unlike the previously reported F1174C/L/V mutations, mutation of F1174 to S sensitizes EML4-ALK variants 3a and 3b to crizotinib. Conclusion: These findings highlight the complexity of drug selection when treating patients harboring resistance mutations and suggest that the F1174S mutation in EML4-ALK variant 1 is likely not a potent oncogenic driver. Additional oncogenic driver or other resistance mechanisms should be considered in the case of EML4-ALK variant 1 with F1174S mutation. [ABSTRACT FROM AUTHOR]

High-risk neuroblastoma (NB) is a significant clinical challenge. MYCN and Anaplastic Lymphoma Kinase (ALK), which are often involved in high-risk NB, lead to increased replication stress in cancer cells, suggesting therapeutic strategies. We previously identified an ATR (ataxia telangiectasia and Rad3-related)/ALK inhibitor (ATRi/ALKi) combination as such a strategy in two independent genetically modified mouse NB models. Here, we identify an underlying molecular mechanism, in which ALK signaling leads to phosphorylation of ATR and CHK1, supporting an effective DNA damage response. The importance of ALK inhibition is supported by mouse data, in which ATRi monotreatment resulted in a robust initial response, but subsequent relapse, in contrast to a 14-d ALKi/ATRi combination treatment that resulted in a robust and sustained response. Finally, we show that the remarkable response to the 14-d combined ATR/ALK inhibition protocol reflects a robust differentiation response, reprogramming tumor cells to a neuronal/Schwann cell lineage identity. Our results identify an ability of ATR inhibition to promote NB differentiation and underscore the importance of further exploring combined ALK/ATR inhibition in NB, particularly in high-risk patient groups with oncogene-induced replication stress. [ABSTRACT FROM AUTHOR]

Teacher attitudes can influence the successful instruction and interventions within the classroom. The present study examined in-service teachers' attitudes toward students with and without autism spectrum disorder in the United States. A total of 234 teachers (pre-Kindergarten to Grade 12) from public and charter schools in a metropolitan city participated in a survey. Participants read two scenarios, one featuring a student displaying autistic symptoms and another featuring a typical student. They then indicated their attitudes toward each student. Results revealed that in-service teachers perceive the student with ASD as more different from typical students and the teachers are more likely to dislike and avoid the student with ASD. Standard regression analysis demonstrated that being female, teaching at the elementary level, and holding special education certification are predictors of a teacher's positive perception of a student with autism spectrum disorder. The implications of these findings for professional practice are discussed.

This article reports findings from a study of an alternative educational program for at-risk secondary students, comparing student perceptions of their public school environment, measured upon intake in the alternative school, with their perceptions of the alternative school environment after four and eight months of attendance in the program. Student perceptions of teacher support in the alternative school environment were significantly more positive than their perceptions of the public school environment. Another purpose was to assess the relation between student perceptions of various aspects of the school environment with specific academic, behavioral, and socioemotional variables. The implications of these findings and future research inquiries are addressed.

Mentored undergraduate research has been identified as a high-impact practice that enhances teaching and learning in higher education. It is reported to influence students' academic, affective, and behavioral outcomes. However, there is only an emerging literature related to student outcomes associated with identity development, specifically students' personal and professional identities. This integrative literature review examines the intersections and interrelationship across mentoring, undergraduate research, and student identity development. Its results uncover the complexity of the constructs, and their dynamic interrelationship, especially when viewed through the lenses of the sociocultural perspective grounded in the notion of mediated action. Two assumptions undergird this perspective: first, that all investigation takes place at the intersection of these constructs with mediated action, not individuals in isolation, as a unit of analysis; and, second, that any study of identity must focus on an understanding of identity as multiple, dynamic, and situated in personal and cultural contexts (institutional, disciplinary, and external community culture and values). Thus, the sociocultural perspective and its underlying assumptions shape the proposed research agenda. This research agenda has the potential to advance current knowledge related to mentored undergraduate research and the confluence of elements that contribute to student personal and cultural identities (academic, disciplinary, and professional). Findings from this work will inform our understanding of learning and knowledge construction in sociocultural context, and the trajectory of identity development of students engaged in high-impact learning experiences.

Simple Summary: The insulin-like growth factor 1 receptor (IGF1R) is a receptor tyrosine kinase (RTK) widely expressed in many cancers, including the pediatric cancer neuroblastoma. Aberrant activation of the anaplastic lymphoma kinase (ALK) RTK by activating point mutations or amplification is identified in 5–12% of neuroblastomas. Here, we investigated IGF1R in ALK-driven neuroblastoma, with the aim of understanding its contribution and exploring its potential for targeted therapy. Using ALK-driven neuroblastoma cell lines, we show that ALK-mutated cells are more sensitive to IGF1R inhibition than ALK-amplified cells, and a synergistic effect is obtained when combining ALK and IGF1R inhibitors. Mechanistically, in ALK-mutated neuroblastoma cells, both ALK and IGF1R contribute significantly to the activation of the downstream PI3K-AKT and RAS-MAPK signaling pathways. Our results suggest that differential activation of signaling downstream of the ALK and IGF1R pathways is in part due to preferential recruitment of adaptor proteins. Aberrant activation of anaplastic lymphoma kinase (ALK) by activating point mutation or amplification drives 5–12% of neuroblastoma (NB). Previous work has identified the involvement of the insulin-like growth factor 1 receptor (IGF1R) receptor tyrosine kinase (RTK) in a wide range of cancers. We show here that many NB cell lines exhibit IGF1R activity, and that IGF1R inhibition led to decreased cell proliferation to varying degrees in ALK-driven NB cells. Furthermore, combined inhibition of ALK and IGF1R resulted in synergistic anti-proliferation effects, in particular in ALK-mutated NB cells. Mechanistically, both ALK and IGF1R contribute significantly to the activation of downstream PI3K-AKT and RAS-MAPK signaling pathways in ALK-mutated NB cells. However, these two RTKs employ a differential repertoire of adaptor proteins to mediate downstream signaling effects. We show here that ALK signaling led to activation of the RAS-MAPK pathway by preferentially phosphorylating the adaptor proteins GAB1, GAB2, and FRS2, while IGF1R signaling preferentially phosphorylated IRS2, promoting activation of the PI3K-AKT pathway. Together, these findings reveal a potentially important role of the IGF1R RTK in ALK-mutated NB and that co-targeting of ALK and IGF1R may be advantageous in clinical treatment of ALK-mutated NB patients. [ABSTRACT FROM AUTHOR]

News avoidance research has been hampered by confusion about how to define and operationalize the concept. Here we intervene in two ongoing debates: first, what is the relationship between selective news avoidance—that is, when people say they sometimes or often avoid news—and overall rates of news consumption? Second, how well do terms intended to distinguish between types of news avoidance based on underlying motivations, such as "intentional" vs. "unintentional" or "news non-use," capture the lived experiences of people who consistently consume little news? We examine these questions using the Reuters Institute's Digital News Report survey data from 46 media markets, as well as interviews with 108 people who consume little-to-no news in the UK, US, and Spain. Survey results show that most people who selectively avoid news consume almost as much news as those who do not, while interviews show that distinguishing types of news avoiders based solely on stated motivations poorly captures how media habits develop through a mix of deliberate choices and socially constructed preferences. We conclude that categorizing news avoiders based on motivations risks misunderstanding the kind of news avoidance that matters most from a normative standpoint: that which is linked with low news consumption. [ABSTRACT FROM AUTHOR]

Anaplastic lymphoma kinase (ALK) fusion variants in Non-Small Cell Lung Cancer (NSCLC) consist of numerous dimerizing fusion partners. Retrospective investigations suggest that treatment benefit in response to ALK tyrosine kinase inhibitors (TKIs) differs dependent on the fusion variant present in the patient tumor. Therefore, understanding the oncogenic signaling networks driven by different ALK fusion variants is important. To do this, we developed controlled inducible cell models expressing either Echinoderm Microtubule Associated Protein Like 4 (EML4)-ALK-V1, EML4-ALK-V3, Kinesin Family Member 5B (KIF5B)-ALK, or TRK-fused gene (TFG)-ALK and investigated their transcriptomic and proteomic responses to ALK activity modulation together with patient-derived ALK-positive NSCLC cell lines. This allowed identification of both common and isoform-specific responses downstream of these four ALK fusions. An inflammatory signature that included upregulation of the Serpin B4 serine protease inhibitor was observed in both ALK fusion inducible and patient-derived cells. We show that Signal transducer and activator of transcription 3 (STAT3), Nuclear Factor Kappa B (NF-kB) and Activator protein 1 (API) are major transcriptional regulators of SERPINB4 downstream of ALK fusions. Upregulation of SERPINB4 promotes survival and inhibits natural killer cell-mediated cytotoxicity, which has potential for therapeutic impact targeting the immune response together with ALK TKIs in NSCLC. [ABSTRACT FROM AUTHOR]

Describes a supervision method that brings together teacher candidates and supervisors to cultivate candidates' disposition toward and ability to construct knowledge. Two case studies illustrate the method, which considers teaching a reflective, inquiry-based, knowledge-producing activity and considers supervision a process where candidate and supervisor move beyond cognitive aspects of instruction to creatively using those within a sociocultural context. (Author/SM)

Addresses clothing-related behavioral problems for public school children and the increasing use of dress codes and uniform policies as preventive measures. It describes dress-related conflicts for black public school students and parents across socialization and contextual settings. The implications of preventive policies and practices are discussed. (GR)

The limits to press freedom in India are usually surveyed from the top-down, with a focus on government efforts to censor journalists, particularly English-language journalists. In this essay, we instead examine India's restrictive press culture by focusing on the sociological workings of Hindi language news production, studying ways in which everyday journalism practices intersect with freedom of expression. The paper first traces the history of Hindi journalism alongside the development of press freedom. It then analyzes mainstream Hindi media coverage of the recent murder and rape of a "lower caste" woman in rural India. Our analysis reveals how the sociological realities of casteism and patriarchy merged with self-censorship to enable media cover up of the rape case. We then draw on interviews with Hindi journalists to illuminate the reasons behind censorship in such cases and in news media more broadly. We argue that a combination of structural, ideological, and historical conditions has limited the growth of press freedom in India. We further suggest that top-down approaches that focus exclusively on English-language media cannot adequately capture the dynamics of news reporting on the ground, and that contemporary news media can only be holistically understood by studying the "non-global," Indian language press. [ABSTRACT FROM AUTHOR]

Author(s): Camilla Englund [1, 3]; Christina E. Lorén [1, 3]; Caroline Grabbe [1]; Gaurav K. Varshney [1]; Fabienne Deleuil [1, 2]; Bengt Hallberg [2]; Ruth H. Palmer (corresponding author) [1] [...]

Background: Neuroblastoma (NB) is one of the most frequently diagnosed tumors in infants. NB is a neuroendocrine tumor type with various characteristics and features, and with diverse outcome. The most malignant NBs have a 5-year survival rate of only 40-50%, indicating the need for novel and improved treatment options. 177Lu-octreotate is routinely administered for treatment of neuroendocrine tumors overexpressing somatostatin receptors (SSTR). The aim of this study was to examine the biodistribution of 177Lu-octreotate in mice bearing aggressive human NB cell lines, in order to evaluate the potential usefulness of 177Lu-octreotate for treatment of NB.Methods: BALB/c nude mice bearing CLB-BAR, CLB-GE or IMR-32 tumor xenografts (n = 5-7/group) were i.v. injected with 0.15 MBq, 1.5 MBq or 15 MBq 177Lu-octreotate and sacrificed 1 h, 24 h, 48 h and 168 h after administration. The radioactivity concentration was determined for collected tissue samples, tumor-to-normal-tissue activity concentration ratios (T/N) and mean absorbed dose for each tissue were calculated. Immunohistochemical (IHC) staining for SSTR1-5, and Ki67 were carried out for tumor xenografts from the three cell lines.Results: High 177Lu concentration levels and T/N values were observed in all NB tumors, with the highest for CLB-GE tumor xenografts (72%IA/g 24 h p.i.; 1.5 MBq 177Lu-octreotate). The mean absorbed dose to the tumor was 6.8 Gy, 54 Gy and 29 Gy for CLB-BAR, CLB-GE and IMR-32, respectively, p.i. of 15 MBq 177Lu-octreotate. Receptor saturation was clearly observed in CLB-BAR, resulting in higher concentration levels in the tumor when lower activity levels where administered. IHC staining demonstrated highest expression of SSTR2 in CLB-GE, followed by CLB-BAR and IMR-32.Conclusion: T/N values for all three human NB tumor xenograft types investigated were high relative to previously investigated neuroendocrine tumor types. The results indicate a clear potential of 177Lu-octreotate as a therapeutic alternative for metastatic NB. [ABSTRACT FROM AUTHOR]

The substrate specificities exhibited by the mammalian phosphatidylinositol (PtdIns) 3-kinase can be changed with cholesterol-based detergents and natural sulfated compounds such as cholesterol sulfate or sulfatide. The specificities are different in vitro and in vivo. The presence of cholesterol sulfate or sulfatide in low concentrations inhibits PtdIns 3-kinase activity. The mammalian PtdIns 3-kinase is a heterodimer with regulatory and catalytic subunits.