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Health professionals may face sexual harassment from patients, faculty, and colleagues. Medicine's hierarchy deters response to sexual harassment. Current evidence consists largely of quantitative data regarding the frequency and types of sexual harassment. More information is needed about the nature of the experience and how or why professionals choose to report or respond.<br />We developed and administered a semistructured interview guide to elicit family medicine faculty and residents' experiences with sexual harassment and gender bias. Facilitators led a series of focus groups divided by faculty (N=28) and residents (N=24). We ensured voluntary consent and groups were audiotaped, transcribed and deidentified. We coded the transcripts using immersion-crystallization theory to identify emergent themes.<br />Sexual harassment from patients and colleagues was described as witnessed or personally experienced by faculty and resident participants in 100% of the focus groups. Respondents identified the presence of mnd faculty is critical. Clarifying the reporting process, having clear expectations for behavior, and a continuum of responses may help increase the frequency of reporting.<br />Only few data are available on treatment-associated behavior of distinct rare CNS-embryonal tumor entities previously treated as "CNS-primitive neuroectodermal tumors" (CNS-PNET). Respective data on specific entities, including CNS neuroblastoma, FOXR2 activated (CNS NB-FOXR2), and embryonal tumor with multi-layered rosettes (ETMR) are needed for development of differentiated treatment strategies.<br />Within this retrospective, international study, tumor samples of clinically well-annotated patients with the original diagnosis of CNS-PNET were analyzed using DNA methylation arrays (n=307). Additional cases (n=66) with DNA methylation pattern of CNS NB-FOXR2 were included irrespective of initial histological diagnosis. Pooled clinical data (n=292) were descriptively analyzed.<br />DNA methylation profiling of "CNS-PNET" classified 58(19%) cases as ETMR, 57(19%) as HGG, 36(12%) as CNS NB-FOXR2, and 89(29%) cases were classified into 18 other entities. Sixty-seven (22%) cases did not show DNA methylation patterns st treatments and a standard-risk-CSI based regimen may be prospectively evaluated. The poor outcome of ETMR across applied treatment strategies substantiates the necessity for evaluation of novel treatments.The multiple myeloma (MM) mutational landscape has identified alterations in KRAS as the most recurring somatic variant. Combining DNA and RNA sequencing, we studied 756 patients and observed KRAS as the most frequently mutated gene in patients at diagnosis; in addition, we demonstrated the persistence or de novo occurrence of the KRAS aberration at disease relapse. Small molecule inhibitors targeting KRAS have been developed; however, they are selective for tumors carrying that KRASG12C mutation. Therefore, there is still a need to develop novel therapeutic approaches to target the KRAS mutational events found in other tumor types, including MM. We have used AZD4785, a potent and selective antisense oligonucleotide (ASO) which selectively targets and down-regulates all KRAS isoforms, as a tool to dissect the functional sequelae secondary to KRAS silencing in MM within the context of the bone marrow niche; and demonstrated its ability to significantly silence KRAS, leading to inhibition of MM tumor growth, both in vitro and in vivo, confirming KRAS as a driver and a therapeutic target in MM.Trained immunity (TI) is a pro-inflammatory program induced in monocyte/macrophages upon sensing of specific pathogens and characterized by immunometabolic and epigenetic changes enhancing cytokine production. Maladaptive activation of TI (i.e., in the absence of infection) might result in detrimental inflammation and disease development; however, the exact role and extent of inappropriate activation of TI in the pathogenesis of human diseases is undetermined. Here, we reveal oncogene-induced, maladaptive induction of TI in the pathogenesis of a human inflammatory myeloid neoplasm (Erdheim-Chester disease, ECD, characterized by the BRAFV600E oncogenic mutation in monocyte/macrophages and excess cytokine production). [https://www.selleckchem.com/products/AZD0530.html AZD0530] Mechanistically, myeloid cells expressing BRAFV600E exhibit all molecular features of TI activation of the AKT/mTOR signaling axis; increased glycolysis, glutaminolysis, and cholesterol synthesis; epigenetic changes on promoters of genes encoding cytokines; and enhanced cytokine production leading to hyper-inflammatory responses. In ECD patients, effective therapeutic strategies contrast this maladaptive TI phenotype; in addition, pharmacologic inhibition of immunometabolic changes underlying TI (i.e., glycolysis) effectively dampens cytokine production by myeloid cells. This study reveals the deleterious potential of inappropriate activation of TI in the pathogenesis of human inflammatory myeloid neoplasms, and the opportunity for inhibition of TI in conditions characterized by maladaptive myeloid-driven inflammation.B- and T- cell acute lymphoblastic leukemia (B/T-ALL) may be refractory or recur after therapy by suppressing host anti-cancer immune surveillance mediated specifically by natural killer (NK) cells. We delineated the phenotypic and functional defects in NK cells of high-risk B/T-ALL patients using mass, flow, and in silico cytometry, with the goal of further elucidating the role of NK cells in sustaining ALL regression. We found that, compared to normal counterparts, NK cells in B/T-ALL patients are less cytotoxic, but exhibit an activated signature characterized by high CD56, high CD69, production of activated NK-origin cytokines, and calcium signaling. We demonstrated that defective maturation of NK cells into cytotoxic effectors prevents NK cells of ALL patients from lysing NK-sensitive targets as efficiently as normal NK cells. Additionally, we showed that NK cells in ALL are exhausted, which is likely caused by their chronic activation. We found that increased frequencies of activated cytokine-producing NK cells are associated with increased disease severity and independently predict poor clinical outcome in ALL patients. Our studies highlight the benefits of developing NK cell profiling as a diagnostic tool to predict clinical outcome in patients with ALL and underscore the clinical potential of allogeneic NK infusions to prevent ALL recurrence.