Bereaved parents' perceptions of memory making: a qualitative meta-synthesis.

OBJECTIVE: This study aims to investigate the experiences of parents who have experienced bereavement in their efforts to preserve memories of their deceased child. METHODS: Employing a qualitative meta-synthesis approach, this study systematically sought relevant qualitative literature by conducting searches across various electronic databases, including PubMed, Embase, CINAHL, PsycINFO, Web of Science, Cochrane Library, and Wiley, up until July 2023. RESULTS: Nine studies are eligible for inclusion and included in the meta-synthesis. Three overarching categories are identified: (1) Affirming the Significance of Memory Making. (2) Best Practices in Memory Making. (3) Barriers to Effective Memory Making. CONCLUSION: Bereaved parents highly value the act of creating lasting memories, emphasizing its profound significance. While forming these memories, it is imperative to offer family-centered care and honor diverse preferences and needs. It is essential to offer effective support to parents, offering them a range of choices. Furthermore, a more comprehensive examination of memory-making practices is required to better understand their influence on parents' recollections of their deceased child.

Identification of CircRNA signature associated with tumor immune infiltration to predict therapeutic efficacy of immunotherapy.

Circular RNAs (circRNAs) play important roles in the regulation of cancer. However, the clinical implications and regulatory networks of circRNAs in cancer patients receiving immune checkpoint blockades (ICB) have not been fully elucidated. Here, we characterize circRNA expression profiles in two independent cohorts of 157 ICB-treated advanced melanoma patients and reveal overall overexpression of circRNAs in ICB non-responders in both pre-treatment and early during therapy. Then, we construct circRNA-miRNA-mRNA regulatory networks to reveal circRNA-related signaling pathways in the context of ICB treatment. Further, we construct an ICB-related circRNA signature (ICBcircSig) score model based on progression-free survival-related circRNAs to predict immunotherapy efficacy. Mechanistically, the overexpression of ICBcircSig circTMTC3 and circFAM117B could increase PD-L1 expression via the miR-142-5p/PD-L1 axis, thus reducing T cell activity and leading to immune escape. Overall, our study characterizes circRNA profiles and regulatory networks in ICB-treated patients, and highlights the clinical utility of circRNAs as predictive biomarkers of immunotherapy.

A Ferroptosis Molecular Subtype-Related Signature for Predicting Prognosis and Response to Chemotherapy in Patients with Chronic Lymphocytic Leukemia.

Ferroptosis is a type of regulated cell death catalyzed by the iron-dependent accumulation of lipid hydroperoxides to lethal levels. Chronic lymphocytic leukemia (CLL) is a chronic lymphoproliferative disorder. However, the understanding of ferroptosis in CLL remains largely poor. In this study, we investigated the stratification and prognostic role of ferroptosis-related genes in CLL patients of ICGC cohort. We obtained fourteen genes with prognostic value by screening 110 ferroptosis-related genes (FRGs). Based on the expression profiles of these 14 genes, we classified CLL patients into two clusters. Most of the FRGs were highly expressed in cluster 1, and cluster 1 was associated with better overall survival (OS). Subsequently, we developed an eight-gene signature (TP63, STEAP3, NQO1, ELAVL1, PRKAA1, HELLS, FANCD2, and CDKN2A) by using LASSO analysis. This risk signature divided CLL patients into high- and low-risk groups. We used Cox regression analysis and ROC analysis demonstrated the risk signature was reliable and robust. And we validated the risk model in an external cohort (GSE22762). We also conducted enrichment analysis and genomic mutation analysis. Finally, we explored the potential effect of chemotherapy between the two risk groups. Our study contributed to understanding the role of ferroptosis in CLL and facilitated personalized and precision treatment.

Variants of neural nitric oxide synthase in the spinal cord of neuropathic rats and their effects on nuclear factor-kappaB (NF-kappaB) activity in PC12 cells.

UNLABELLED: Neuropathic pain due to nerve injury is associated with overactivity of spinal N-methyl-D-aspartate (NMDA) receptors and nitric oxide synthases (NOS). Spinal NOS and NMDA receptors could act in a concerted manner to excite each other in nociceptive signaling. Among the 3 major NOS isoforms, neuronal NOS (nNOS) has the most functional relationship with NMDA receptors through a PDZ-PDZ (PSD-95, Dlg, ZO-1 homology) postsynapse interaction. However, some nNOS variants lack the PDZ domain, which may result in the changes in the interaction with the NMDA receptor and subsequent localization and enzymatic activity. The aim of this study was to determine which nNOS variants are expressed in the spinal cord in neuropathic rats and deduce their role in neuropathic pain by testing the effects of these kinds of nNOS on nuclear factor-kappaB (NF-kappaB) activity in PC12 cells. Western blot analysis revealed that there were at least 3 bands of nNOS (155, 135, and 125 kDa) in the spinal cord and, moreover, that nNOS at 135 kDa decreased significantly after development of neuropathic pain. 5'-RACE-PCR and Southern blots determined that the nNOS at 155 and 135 kDa corresponded to nNOSalpha and nNOSbeta, respectively, which was confirmed by RT-PCR. PC12 cells transfected with the nNOSalpha gene had no effect on NF-kappaB activity, but nNOSbeta without the PDZ domain significantly decreased that in PC12 cells. Considering the importance of spinal NF-kappaB signaling in neuropathic rat, it could be concluded that changes in spinal nNOS variants and quantity after peripheral nerve injury implicate nNOS in the generation of neuropathic pain. PERSPECTIVE: This article presents data demonstrating that nNOS variants change in the spinal cord of the rats after neuropathic pain and result in differential effects on NF-kappaB activity in PC12 cells. These changes in nNOS variants and their different characteristics may account for the spinal NO paradox role in neuropathic pain. Furthermore, these data suggest that nNOSbeta may represent a new therapeutic target for the treatment of chronic neuropathic pain.