Anaplastic lymphocyte kinase (ALK) rearrangement, a key oncogenic driver promoting the expression of ALK protein in tumor cells, is found in 2%-7% of patients with nonsmall cell lung cancer (NSCLC). ALK fusion is routinely determined with immunohistochemistry (IHC) or RT-PCR in many laboratories. However, there were discordant cases. In this study, we employed a hybridization-based next-generation sequencing (NGS) of DNA and RNA to explore the underlying mechanisms. FFPE tissues of 302 NSCLC tumors, which had been ALK tested with IHC and RT-PCR, were retrospectively studied, of which 18 were IHC positive, and 14 were RT-PCR positive. This resulted in 4 discordant cases, which were further analyzed with NGS. One sample failed the RNA quality control due to extensive RNA degradation. Three non-EML4-ALK fusions were identified in the 4 cases with DNA sequencing, including a CLTC-ALK fusion (EX31EX19), a WDPCP-ALK fusion (EX14EX20), and a novel PLB1-ALK fusion (EX6EX20). Interestingly, two additional fusions STRN-ALK fusion (EX3EX20) and DCTN1-ALK fusion (EX20EX20), were identified with RNA sequencing. The discordance of IHC/RT-PCR was mainly due to limited coverage of non-EML4-ALK fusions in the RT-PCR assay. NGS-based DNA/RNA sequencing appears to be a promising rescue technique for nonclear-cut IHC/RT-PCR cases and also offers a unique opportunity to identify novel ALK fusions.Targetable kinase fusions are extremely rare ( less then 1%) in colorectal cancers (CRCs), making their diagnosis challenging and often underinvestigated. They have been shown particularly frequently among MSI-High, BRAF/KRAS/NRAS wild-type CRCs with MLH1 loss (MLH1loss MSI-High wild-type). We searched for NTRK1, NTRK2, NTRK3, ALK, ROS1, BRAF, RET, and NRG1 kinase fusions in CRCs using methods easy-to-implement in pathology laboratories immunohistochemistry (IHC), fluorescent in situ hybridization (FISH), and fully automated real-time PCR targeted analyses. RNA-sequencing analyses were used for confirmation. Among 84 selected MLH1 deficient (IHC) CRCs cases, MLH1loss MSI-High wild-type CRCs consisted first in 19 cases after Idylla™ analyses and finally in 18 cases (21%) after RNA-sequencing (detection of one additional KRASG12D mutation). FISH (and when relevant, IHC) analyses concluded in 5 NTRK1, 3 NTRK3, 1 ALK, 2 BRAF, and 2 RET FISH positive tumors. ALK and NTRK1 rearranged tumors were IHC positive, but pan-TRK IHC was negative in the 3 NTRK3 FISH positive tumors. RNA-sequencing analyses confirmed 12 of 13 fusions with only one false positive RET FISH result. Finally, 12/18 (67%) of MLH1loss MSI-High wild-type CRCs contained targetable kinase fusions. Our study demonstrates the feasibility, but also the cost-effectiveness, of a multistep but rapid diagnostic strategy based on nonsequencing methods to identify rare and targetable kinase fusions in patients with advanced CRCs, as well as the high prevalence of these kinase fusions in MLH1loss MSI-High wild-type CRCs. Nevertheless, confirmatory RNA-sequencing analyses are necessary in case of low FISH positive nuclei percentage to rule out FISH false-positive results.Oral corticosteroid (OCS) use in severe asthma remains all too common despite advances in asthma treatment. Use of OCS is associated with significant toxicity that can have a lasting adverse impact on a patient's overall health. Monoclonal antibodies have been developed that reduce both the rate of occurrence of OCS-treated exacerbations and the OCS requirements in patients with oral corticosteroid-dependent asthma. This article describes strategies to prevent and best manage endocrine complications associated with OCS use and provides guidance on OCS dose management after the introduction of steroid-sparing therapies. (1) We identify OCS-dependent patients and assess for comorbidities including bone health, glycemic control, and adrenal function; (2) we begin attempts at OCS dose optimization before or soon after introducing a steroid-sparing biologic therapy; (3) we taper OCS, using explicit criteria for asthma control; (4) we assess hypothalamic-pituitary-adrenal axis integrity once a physiologic dose of OCS is achieved to guide further the rate of OCS taper; and (5) we manage corticosteroid-related comorbidities as detailed in this article.Children with asthma grow to become adults with asthma. Adolescents are not simply older children and do not automatically transform into independent adults, nor do they become proficient in self-management of their condition overnight. Adolescence is a high-risk time for many people with asthma, with increased risk of asthma-related morbidity and mortality. Children with high-risk asthma attend hospital-based asthma clinics with their parents until they reach young adulthood, and parents usually take on the significant burden of disease management on behalf of their children. Once patients are transferred to adult medical teams, many will continue to have limited knowledge about their asthma, limited understanding of how to manage their symptoms and comorbidities, and limited comprehension of how and why to take their regular medication.  https://www.selleckchem.com/products/bozitinib.html  Adolescence is a critical time of change during which young people yearn for autonomy. Effective transition gives young people the skills and knowledge necessary to manage their health independently and provides the substrate for autonomous care, the bed rock of long-term conditions. This review focuses on the challenges of adolescent health care and provides guidance on how to take a planned, patient-centered approach to ensure each transition is effective and safe.Bongkrekic acid (BKA) produced by pseudomonas cocovenenans is a deadly toxin, and is mainly found in spoiled or fermented foods. However, less is known on its immunotoxicity. Neutrophil extracellular traps (NETs) are a novel effector mechanism of neutrophils against invading pathogens, but excessive NETs also contribute to tissue damage. This study aimed to investigate NET formation triggered by BKA in murine neutrophils, and describe its characteristics and potential mechanisms. Our results showed that BKA triggered NET formation via co-localization of DNA and histone or MPO by immunostaining. Moreover, BKA-triggered NET formation was dose- and time-dependent via NET quantification based on Picogreen-derived fluorescence intensities. Furthermore, BKA increased ROS production in neutrophils. Pharmacological inhibition indicated that BKA-triggered NET formation was associated with ROS-p38 and -ERK signaling pathways, but independent on NADPH oxidase. Besides, PAD4 and P2X1 receptor also mediated BKA-triggered NET formation.