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Honeybees require an efficient immune system to defend against microbial pathogens. The American foulbrood pathogen, Paenibacillus larvae, is lethal to honeybees and one of the main causes of colony collapse. This study investigated the immune responses of Apis mellifera and Apis cerana honeybees against the bacterial pathogen P. larvae. Both species of honeybee larvae exhibited significant mortality even at 102 103 cfu/mL of P. larvae by diet-feeding, although A. mellifera appeared to be more tolerant to the bacterial pathogen than A. cerana. Upon bacterial infection, the two honeybee species expressed both cellular and humoral immune responses. Hemocytes of both species exhibited characteristic spreading behaviors, accompanied by cytoskeletal extension along with F-actin growth, and formed nodules. Larvae of both species also expressed an antimicrobial peptide called apolipophorin III (ApoLpIII) in response to bacterial infection. However, these immune responses were significantly suppressed by a specific inhibitor to phospholipase A2 (PLA2). Each honeybee genome encodes four PLA2 genes (PLA2A ~ PLA2D), representing four orthologous combinations between the two species. In response to P. larvae infection, both species significantly up-regulated PLA2 enzyme activities and the expression of all four PLA2 genes. To determine the roles of the four PLA2s in the immune responses, RNA interference (RNAi) was performed by injecting gene-specific double stranded RNAs (dsRNAs). All four RNAi treatments significantly suppressed the immune responses, and specific inhibition of the two secretory PLA2s (PLA2A and PLA2B) potently suppressed nodule formation and ApoLpIII expression. These results demonstrate the cellular and humoral immune responses of A. mellifera and A. cerana against P. larvae. This study suggests that eicosanoids play a crucial role in mediating common immune responses in two closely related honeybees., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Jin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Mesenchymal-epidermal transition factor gene amplification ( MET amp) is being investigated as a therapeutic target in advanced non-small cell lung cancer (NSCLC). We reviewed the epidemiology and disease characteristics associated with primary and secondary MET amp, as well as the testing procedures used to identify MET amp, in advanced NSCLC. Economic and humanistic burdens, and the practice patterns and treatments under investigation for MET amp were also examined., Methods: Embase and Medline (via ProQuest), ClinicalTrials.gov, and Cochrane Controlled Register of Trials (2015-2022) were systematically searched. Conference abstracts were searched via Embase and conference proceedings websites (2020-2022). The review focused on evidence from the United States; global evidence was included for identified evidence gaps., Results: The median rate of primary MET amp in NSCLC across the references was 4.8% (n=4 studies) and of secondary MET amp (epidermal growth factor receptor [ EGFR ]-mutant NSCLC) was 15% (n=10). Next-generation sequencing (NGS; n=12) and/or fluorescence in situ hybridization (FISH; n=11) were most frequently used in real-world studies and FISH testing most frequently used in clinical trials (n=9/10). MET amp definitions varied among clinical trials using ISH/FISH testing (MET to chromosome 7 centromere ratio of ≥1.8 to ≥3.0; or gene copy number [GCN] ≥5 to ≥10) and among trials using NGS (tissue testing: GCN ≥6; liquid biopsy: MET copy number ≥2.1 to >5). Limited to no data were identified on the economic and humanistic burdens, and real-world treatment of MET amp NSCLC. Promising preliminary results from trials enrolling patients with EGFR -mutated, MET amp advanced NSCLC progressing on an EGFR-tyrosine kinase inhibitor (TKI) were observed with MET-TKIs (i.e., tepotinib, savolitinib, and capmatinib) in combination with EGFR-TKIs (i.e., gefitinib and osimertinib). For metastatic NSCLC and high-level MET amp, monotherapy with capmatinib, crizotinib, and tepotinib are recommended in the 2022 published NSCLC NCCN Guidelines., Conclusion: Primary MET amp occurs in approximately 5% of NSCLC cases, and secondary MET amp in approximately 15% of cases previously treated with an EGFR inhibitor. Variability in testing methods (including ISH/FISH and NGS) and definitions were observed. Several treatments are promising in treating MET amp NSCLC. Additional studies evaluating the clinical, economic, and humanistic burdens are needed., Competing Interests: Authors MY, FL, and RH were employed by the company EMD Serono, Inc., Rockland, MA, USA, an affiliate of Merck KGaA, at the time of the study. Authors EM and BL were employed by the company OPEN Health at the time of this study, which was the recipient of consulting fees from EMD Serono, Inc., Rockland, MA, USA, an affiliate of Merck KGaA. Author RS received honoraria from AstraZeneca, and Amgen; attended advisory boards and provided consulting for AstraZeneca, EMD Serono, Inc., Rockland, MA, USA, an affiliate of Merck KGaA, Daiichi Sankyo, Lilly, Janssen Oncology, Macrogenics, Sanofi/Aventis, Regeneron, Mirati Therapeutics, and GlaxoSmithKline; received research funding from Merck, AstraZeneca Investigator-sponsored trials, and BMS Institution research funding., (Copyright © 2024 Yang, Mandal, Liu, O’Hara, Lesher and Sanborn.)

Background: The relation between shyness and self-esteem in women has not been fully elucidated. Shyness is a source of many problems in social interactions, although it may be positively evaluated by women as a stereotypically female trait. The aim of the study was to examine relations between shyness, self-esteem, its dimensions, and contingencies of self-worth in women. It also compared the self-esteem and contingencies of self-worth in shy and bold women., Participants and Procedure: The study was conducted in a sample of 1020 Polish women, aged 18-73. The Revised Cheek and Buss Shyness Scale, the Multidimensional Self-Esteem Inventory, and the Contingencies of Self-Worth Scale were used., Results: The results of linear multiple regression showed that predictors of shyness were dimensions of self-esteem related to likeability, personal power, lovability, body functioning, academic/professional competences, and self-worth conditioned by others' approval and God's love. Shy women had significantly lower global self-esteem in comparison to bold women. Shy women evaluated themselves lower than bold women did, in all the dimensions of self-esteem. Both shy and bold women find family support and academic/professional competencies the main contingencies of self-worth, and God's love was indicated the least., Conclusions: The results illustrated the importance of shyness for women's self-esteem, and also have implications for understanding how shy and bold women may express themselves in social life., Competing Interests: The author declares no conflict of interest., (Copyright © Institute of Psychology, University of Gdansk.)

Background: Mindfulness is a specific state of attention which involves a constant focus on what is happening at the present time in a way that is neither judgmental nor evaluative. The aim of this study was to investigate the importance of mindfulness for relationship quality and conflict resolution strategies in close relationships. Five components of mindfulness were examined: observing, describing, acting with awareness, nonjudging, and nonreactivity., Participants and Procedure: The study included 153 participants (79 women, 74 men; aged 19-60 years). 39.2% of the respondents were married, 20.9% were engaged, 39.9 were in romantic relationships. The mean duration of the close relationship was 6.25 years. The following measures were used: the Five Facet Mindfulness Questionnaire, the Patterns of Problem Solving Questionnaire, and the Dyadic Adaptation Scale., Results: Acting with awareness, dialogue and avoiding conflict escalation strategy were predictors of relationship quality. The relationship status (marriage and engagement) was also a predictor of relationship quality. Gender, age, and duration of the relationship were not predictors of relationship quality. The results showed correlation between mindfulness and relationship quality ( r = .28). There was a positive correlation between nonjudging and satisfaction in the relationship and between describing and emotional expression. Also, there was a negative correlation between nonreactivity and compatibility. Mindfulness was positively correlated with dialogue and negatively correlated with escalation of and withdrawal from a conflict., Conclusions: Mindfulness is important to the relationship's quality and conflict resolution strategies. Among the components of mindfulness, especially acting with awareness is important to relationship quality., (Copyright © Institute of Psychology, University of Gdansk.)