Aims
This study explored how adult children perceived family resilience, barriers to develop family resilience and how cultural values influence their experience of parents with bipolar disorder in ...Chinese society.
Design
A qualitative design with an interpretive phenomenological analysis of data was employed.
Methods
Twenty adults who had lived with parents with bipolar disorder during childhood were recruited from the acute psychiatric ward when their parents were admitted to the hospital. They described their experiences of perceived family resilience and barriers to resilience (October 2013–September 2015). Semi‐structured interviews were conducted in the hospital meeting room or at a convenient location.
Findings
Six themes were identified in family resilience: ill parents try to be good parents, parents’ personal strengths, parents’ positive attitudes towards mental illness, flexibility of family role, cohesive relationships between family members, and families’ social connections. Three themes were identified in the barriers to develop family resilience: poor parenting/family function, conflict between parents and poor mental health literacy.
Conclusion
Children's views of family resilience could transform their suffering from lived experiences with a mentally ill parent to a positive growth experience. Family resilience includes well and ill parents’ efforts and social network's help to maintain family function. However, the conflicts between well and ill parents and poor family function result in a traumatic growth experience.
Impact
To enhance a positive growth experience, family resilience programs for a parent with bipolar disorder aiming to cultivate both the ill and well parents’ inner strength and their competence of parenting skills with connecting their social network to maintain family function is needed. Moreover, early stress‐reduction intervention needs to be developed for children who did not experience family resilience.
Virus-encoded microRNAs (miRNAs) have been shown to regulate a variety of biological processes involved in viral infection and viral-associated pathogenesis. Epstein-Barr virus (EBV) is a herpesvirus ...implicated in nasopharyngeal carcinoma (NPC) and other human malignancies. EBV-encoded miRNAs were among the first group of viral miRNAs identified. To understand the roles of EBV miRNAs in the pathogenesis of NPC, we utilized deep sequencing technology to characterize the EBV miRNA transcriptome in clinical NPC tissues. We obtained more than 110,000 sequence reads in NPC samples and identified 44 EBV BART miRNAs, including four new mature miRNAs derived from previously identified BART miRNA precursor hairpins. Further analysis revealed extensive sequence variations (isomiRs) of EBV miRNAs, including terminal isomiRs at both the 5' and 3' ends and nucleotide variants. Analysis of EBV genomic sequences indicated that the majority of EBV miRNA nucleotide variants resulted from post-transcriptional modifications. Read counts of individual EBV miRNA in NPC tissue spanned from a few reads to approximately 18,000 reads, confirming the wide expression range of EBV miRNAs. Several EBV miRNAs were expressed at levels similar to highly abundant human miRNAs. Sequence analysis revealed that most of the highly abundant EBV miRNAs share their seed sequences (nucleotides 2-7) with human miRNAs, suggesting that seed sequence content may be an important factor underlying the differential accumulation of BART miRNAs. Interestingly, many of these human miRNAs have been found to be dysregulated in human malignancies, including NPC. These observations not only provide a potential linkage between EBV miRNAs and human malignancy but also suggest a highly coordinated mechanism through which EBV miRNAs may mimic or compete with human miRNAs to affect cellular functions.
Genetic alterations for epithelial ovarian cancer are insufficiently characterized. Previous studies are limited regarding included histologies, gene numbers, copy number variant (CNV) detection, and ...interpretation of pathway alteration patterns of individual patients.
We sequenced 410 genes to analyze mutations and CNV of 82 ovarian carcinomas, including high-grade serous (n = 37), endometrioid (n = 22) and clear cell (n = 23) histologies. Eligibility for targeted therapy was determined for each patient by a pathway-based approach. The analysis covered DNA repair, receptor tyrosine kinase, PI3K/AKT/MTOR, RAS/MAPK, cell cycle, and hedgehog pathways, and included 14 drug targets.
Postulated PARP, MTOR, and CDK4/6 inhibition sensitivity were most common. BRCA1/2 alterations, PTEN loss, and gain of PIK3CA and CCND1 were characteristic for high-grade serous carcinomas. Mutations of ARID1A, PIK3CA, and KRAS, and ERBB2 gain were enriched in the other histologies. PTEN mutations and high tumor mutational burden were characteristic for endometrioid carcinomas. Drug target downstream alterations impaired actionability in all histologies, and many alterations would not have been discovered by key gene mutational analysis. Individual patients often had more than one actionable drug target.
Genetic alterations in ovarian carcinomas are complex and differ among histologies. Our results aid the personalization of therapy and biomarker analysis for clinical studies, and indicate a high potential for combinations of targeted therapies.
The rice SUB1A-1 gene, which encodes a group VII ethylene response factor (ERFVII), plays a pivotal role in rice survival under flooding stress, as well as other abiotic stresses. In Arabidopsis, ...five ERFVII factors play roles in regulating hypoxic responses. A characteristic feature of Arabidopsis ERFVIIs is a destabilizing N terminus, which functions as an N-degron that targets them for degradation via the oxygen-dependent N-end rule pathway of proteolysis, but permits their stabilization during hypoxia for hypoxia-responsive signaling. Despite having the canonical N-degron sequence, SUB1A-1 is not under N-end rule regulation, suggesting a distinct hypoxia signaling pathway in rice during submergence. Herein we show that two other rice ERFVIIs gene, ERF66 and ERF67, are directly transcriptionally up-regulated by SUB1A-1 under submergence. In contrast to SUB1A-1, ERF66 and ERF67 are substrates of the N-end rule pathway that are stabilized under hypoxia and may be responsible for triggering a stronger transcriptional response to promote submergence survival. In support of this, overexpression of ERF66 or ERF67 leads to activation of anaerobic survival genes and enhanced submergence tolerance. Furthermore, by using structural and protein-interaction analyses, we show that the C terminus of SUB1A-1 prevents its degradation via the N-end rule and directly interacts with the SUB1A-1 N terminus, which may explain the enhanced stability of SUB1A-1 despite bearing an N-degron sequence. In summary, our results suggest that SUB1A-1, ERF66, and ERF67 form a regulatory cascade involving transcriptional and N-end rule control, which allows rice to distinguish flooding from other SUB1A-1–regulated stresses.
Abstract
To predict natural ureter lengths based on clinical images. We reviewed our image database of patients who underwent multiphasic computed tomography urography from January 2019 to April ...2020. Natural ureteral length (UL
CTU
) was measured using a three-dimensional curved multiplanar reformation technique. Patient parameters including age, height, and height of the lumbar spine, the index of ureteral length using kidney/ureter/bladder (KUB) radiographs (C-P and C-PS) and computed tomography (UL
CT
) were collected. UL
CTU
correlated most strongly with UL
CT
. R square and adjusted R square values from multivariate regression were 0.686 and 0.678 (left side) and 0.516 and 0.503 (right side), respectively. UL
CTU
could be estimated by the regression model in three different scenarios as follows:
UL
CT
+ C-P
UL
CTUL
= 0.405
$$\times$$
×
UL
CTL
$$+$$
+
0.626
$$\times$$
×
C-P
L
– 0.508 cm
UL
CTUR
= 0.558
$$\times$$
×
UL
CTR
$$+$$
+
0.218
$$\times$$
×
C-P
R
+ 6.533 cm
UL
CT
UL
CTUL
= 0.876
$$\times$$
×
UL
CTL
$$+$$
+
6.337 cm
UL
CTUR
= 0.710
$$\times$$
×
UL
CTR
$$+$$
+
9.625 cm
C-P
UL
CTUL
= 0.678
$$\times$$
×
C-P
L
$$+$$
+
4.836 cm
UL
CTUR
= 0.495
$$\times$$
×
C-P
R
$$+$$
+
10.353 cm
We provide equations to predict UL
CTU
based on CT, KUB or CT plus KUB for different clinical scenarios. The formula based on CT plus KUB provided the most accurate estimation, while the others had lower validation values but could still meet clinical needs.
Recently, increasing data show that immunotherapy could be a powerful weapon against cancers. Comparing to the traditional surgery, chemotherapy or radiotherapy, immunotherapy more specifically ...targets cancer cells, giving rise to the opportunities to the patients to have higher response rates and better quality of life and even to cure the disease. Cancer vaccines could be designed to target tumor-associated antigens (TAAs), cancer germline antigens, virus-associated antigens, or tumor-specific antigens (TSAs), which are also called neoantigens. The cancer vaccines could be cell-based (e.g., dendritic cell vaccine provenge (sipuleucel-T) targeting prostatic acid phosphatase for metastatic prostate cancer), peptide/protein-based, or gene- (DNA/RNA) based, with the different kinds of adjuvants. Neoantigens are tumor-specific and could be presented by MHC molecules and recognized by T lymphocytes, serving the ideal immune targets to increase the therapeutic specificity and decrease the risk of nonspecific autoimmunity. By targeting the shared antigens and private epitopes, the cancer vaccine has potential to treat the disease. Accordingly, personalized neoantigen-based immunotherapies are emerging. In this article, we review the literature and evidence of the advantage and application of cancer vaccine. We summarize the recent clinical trials of neoantigen cancer vaccines which were designed according to the patients’ personal mutanome. With the rapid development of personalized immunotherapy, it is believed that tumors could be efficiently controlled and become curable in the new era of precision medicine.
Aims and Objectives
This study examined the changes in patients' parental functioning and the associated factors, including manic, depressive symptoms and social support from before discharge to 6 ...months post‐discharge.
Background
For parents with bipolar disorder and major depression, parenting is a recovery factor for patients, but little research examines the dynamic parental functioning from acute hospitalisation to a remission stage.
Design
A longitudinal design was used. The STROBE Checklist were used in presenting this research.
Methods
Participants were inpatients with bipolar disorder or major depression (n = 33) recruited within one week before discharge from the acute psychiatric ward in Taiwan. Data on parental functioning was collected four times: before discharge (T1), the 1st (T2), the 3rd (T3) and the 6th (T4) months of post‐discharge. Baseline parental functioning before admitting to the acute word was retrospectively assessed at T0. The questionnaires included positive and negative domains of parenting practice, hypomanic/manic symptoms, depressive symptoms and social support. Generalised estimating equations were applied for data analysis.
Results
The negative parenting domains (poor monitoring, inconsistent discipline) decreased during hospitalisation but increased at one month post‐discharge, except corporal punishment at 3‐months discharge. The positive parenting domains (parental involvement and nurturance/responsiveness) did not recovery to baseline. While clinical symptoms remained stable during 6 months post‐discharge, social support decreased at 3 and 6 months post‐discharge. Higher depressive symptoms and low social support were associated with positive parenting domains but not related to negative parenting domains. Manic symptoms were not associated with positive or negative parenting domains.
Conclusions
Positive parenting domains did not fully return to the usual situation during 6 months post‐discharge.
Relevance to clinical practice
Parenting functioning recovery program targeting at the impacts of depressive symptoms on the parenting functioning and insufficient social support is needed from hospitalisation to post‐discharge.
MicroRNAs (miRNAs) are a family of small RNA molecules that negatively regulate the expression of protein-coding genes and play critical roles in orchestrating diverse cellular processes. This ...regulatory mechanism is also exploited by viruses to direct their life cycle and evade the host immune system. Epstein-Barr virus (EBV) is an oncogenic virus that is closely associated with multiple human diseases, including nasopharyngeal carcinoma (NPC), which is a highly metastatic type of tumor and is frequently reported in South Asia. Several viral proteins have been found to promote the migration and invasiveness of NPC cells. However, not all tumor tissues express these viral oncoproteins, suggesting that other mechanisms may contribute to the aggressive behavior of NPC tumor cells. A previous sequencing study by our group revealed that the EBV miRNA miR-BART9 was expressed at high levels in all EBV-positive NPC tissues. In the present study, we used gain- and loss-of-function approaches to investigate the effect of miR-BART9 in EBV-negative and EBV-positive NPC cells. We discovered that miR-BART9 promotes the migration and invasiveness of cultured NPC cells. The promigratory activity observed in vitro was manifested as an enhanced metastatic ability in vivo. Computational analysis revealed that miR-BART9 may target E-cadherin, a membrane protein that is pivotal in preserving cell-cell junctions and the epithelial phenotype. Through biochemical assays and functional rescue analysis, we confirmed that miR-BART9 specifically inhibits E-cadherin to induce a mesenchymal-like phenotype and promote the migration of NPC cells. These results indicated that miR-BART9 is a prometastatic viral miRNA and suggested that high levels of miR-BART9 in EBV-positive NPC cells may contribute to the aggressiveness of tumor cells.
Transient receptor potential melastatin channel subfamily member 2 (TRPM2) has an essential function in cell survival and is highly expressed in many cancers. Inhibition of TRPM2 in neuroblastoma by ...depletion with CRISPR technology or expression of dominant negative TRPM2-S has been shown to significantly reduce cell viability. Here, the role of proline-rich tyrosine kinase 2 (Pyk2) in TRPM2 modulation of neuroblastoma viability was explored. In TRPM2-depleted cells, phosphorylation and expression of Pyk2 and cAMP-responsive element-binding protein (CREB), a downstream target, were significantly reduced after application of the chemotherapeutic agent doxorubicin. Overexpression of wild-type Pyk2 rescued cell viability. Reduction of Pyk2 expression with shRNA decreased cell viability and CREB phosphorylation and expression, demonstrating Pyk2 modulates CREB activation. TRPM2 depletion impaired phosphorylation of Src, an activator of Pyk2, and this may be a mechanism to reduce Pyk2 phosphorylation. TRPM2 inhibition was previously demonstrated to decrease mitochondrial function. Here, CREB, Pyk2, and phosphorylated Src were reduced in mitochondria of TRPM2-depleted cells, consistent with their role in modulating expression and activation of mitochondrial proteins. Phosphorylated Src and phosphorylated and total CREB were reduced in TRPM2-depleted nuclei. Expression and function of mitochondrial calcium uniporter (MCU), a target of phosphorylated Pyk2 and CREB, were significantly reduced. Wild-type TRPM2 but not Ca
-impermeable mutant E960D reconstituted phosphorylation and expression of Pyk2 and CREB in TRPM2-depleted cells exposed to doxorubicin. Results demonstrate that TRPM2 expression protects the viability of neuroblastoma through Src, Pyk2, CREB, and MCU activation, which play key roles in maintaining mitochondrial function and cellular bioenergetics.
We surveyed differential gene expression patterns during early photomorphogenesis in both wild-type and mutant Arabidopsis defective in HY5, an influential positive regulator of the responses of gene ...expression to a light stimulus, to identify light-responsive genes whose expression was HY5 dependent. These gene-expression data identified light-regulated zinc finger protein 1 (LZF1), a gene encoding a previously uncharacterized C2C2-CO B-box transcriptional regulator. HY5 has positive trans-activating activity toward LZF1 and binding affinity to LZF1 promoter in vivo. HY5 is needed but not sufficient for the induction of LZF1 expression. Anthocyanin content is significantly diminished in lzf1 under far red, which is the most efficient light for the induction of LZF1. The expression of PAP1/MYB75 is elevated in plants overexpressing LZF1, which leads to the hyperaccumulation of anthocyanin in transgenic Arabidopsis. The transition from etioplast to chloroplast and the accumulation of chlorophyll were notably compromised in the lzf1 mutant. We provide molecular evidence that LZF1 influences chloroplast biogenesis and function via regulating genes encoding chloroplast proteins. In the absence of HY5, mutation of LZF1 leads to further reduced light sensitivity for light-regulated inhibition of hypocotyl elongation and anthocyanin and chlorophyll accumulation. Our data indicate that LZF1 is a positive regulator functioning in Arabidopsis de-etiolation.
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