The C-degron pathway eliminates mislocalized proteins and products of deubiquitinating enzymes.

Protein termini are determinants of protein stability. Proteins bearing degradation signals, or degrons, at their amino- or carboxyl-termini are eliminated by the N- or C-degron pathways, respectively. We aimed to elucidate the function of C-degron pathways and to unveil how normal proteomes are exempt from C-degron pathway-mediated destruction. Our data reveal that C-degron pathways remove mislocalized cellular proteins and cleavage products of deubiquitinating enzymes. Furthermore, the C-degron and N-degron pathways cooperate in protein removal. Proteome analysis revealed a shortfall in normal proteins targeted by C-degron pathways, but not of defective proteins, suggesting proteolysis-based immunity as a constraint for protein evolution/selection. Our work highlights the importance of protein termini for protein quality surveillance, and the relationship between the functional proteome and protein degradation pathways.

A novel HIF1α-STIL-FOXM1 axis regulates tumor metastasis.

BACKGROUND: Metastasis is the major cause of morbidity and mortality in cancer that involves in multiple steps including epithelial-mesenchymal transition (EMT) process. Centrosome is an organelle that functions as the major microtubule organizing center (MTOC), and centrosome abnormalities are commonly correlated with tumor aggressiveness. However, the conclusive mechanisms indicating specific centrosomal proteins participated in tumor progression and metastasis remain largely unknown. METHODS: The expression levels of centriolar/centrosomal genes in various types of cancers were first examined by in silico analysis of the data derived from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and European Bioinformatics Institute (EBI) datasets. The expression of STIL (SCL/TAL1-interrupting locus) protein in clinical specimens was further assessed by Immunohistochemistry (IHC) analysis and the oncogenic roles of STIL in tumorigenesis were analyzed using in vitro and in vivo assays, including cell migration, invasion, xenograft tumor formation, and metastasis assays. The transcriptome differences between low- and high-STIL expression cells were analyzed by RNA-seq to uncover candidate genes involved in oncogenic pathways. The quantitative polymerase chain reaction (qPCR) and reporter assays were performed to confirm the results. The chromatin immunoprecipitation (ChIP)-qPCR assay was applied to demonstrate the binding of transcriptional factors to the promoter. RESULTS: The expression of STIL shows the most significant increase in lung and various other types of cancers, and is highly associated with patients' survival rate. Depletion of STIL inhibits tumor growth and metastasis. Interestingly, excess STIL activates the EMT pathway, and subsequently enhances cancer cell migration and invasion. Importantly, we reveal an unexpected role of STIL in tumor metastasis. A subset of STIL translocate into nucleus and associate with FOXM1 (Forkhead box protein M1) to promote tumor metastasis and stemness via FOXM1-mediated downstream target genes. Furthermore, we demonstrate that hypoxia-inducible factor 1α (HIF1α) directly binds to the STIL promoter and upregulates STIL expression under hypoxic condition. CONCLUSIONS: Our findings indicate that STIL promotes tumor metastasis through the HIF1α-STIL-FOXM1 axis, and highlight the importance of STIL as a promising therapeutic target for lung cancer treatment.

Internet of Things: Development Intelligent Programmable IoT Controller for Emerging Industry Applications.

The Internet of Things (IoT) has become critical to the implementation of Industry 4.0. The successful operation of smart manufacturing depends on the ability to connect everything together. In this research, we applied the TOC (Theory of Constraints) to develop a wireless Wi-Fi intelligent programmable IoT controller that can be connected to and easily control PLCs. By applying the TOC-focused thinking steps to break through their original limitations, the development process guides the user to use the powerful and simple flow language process control syntax to efficiently connect to PLCs and realize the full range of IoT applications. Finally, this research uses oil-water mixer equipment as the target of continuous improvement and verification. The verification results meet the requirements of the default function. The IoT controller developed in this research uses a marine boiler to illustrate the application. The successful development of flow control language by TOC in this research will enable academic research on PLC-derivative applications. The results of this research will help more SMEs to move into smart manufacturing and the new realm of Industry 4.0.

Can the Paro be my Buddy? Meaningful experiences from the perspectives of older adults.

This study aimed to explore meaningful experiences of older Taiwanese adults who had received a Paro (social robot) companion. Semi-structured qualitative interviews elicited the perspectives of 25 older adults living in a long-term care facility after they had interacted with an individual Paro companion for 8 weeks. Thematic analysis was used in this study as it allows for rich, detailed, and complex descriptions of qualitative data. Analysis identified four themes: Bridging my social bonds; Acting as a comfort Buddy; Relieving my emotional distress; and Encountering Paro with distancing. Although Paro's functioning has some limits, such as lacking speech, most participants expressed that the experience was positive. These findings revealed that the meaningful experiences expressed by participants at the end of the intervention with Paro might provide the value of companionship and improve interpersonal relationships for older adults in geriatric nursing.

The Impact of Engagement with the PARO Therapeutic Robot on the Psychological Benefits of Older Adults with Dementia.

OBJECTIVES: This study aimed to examine the effect of 8-weeks of a 60-minute PARO intervention to reduce depressive symptoms and loneliness in older adults with dementia and investigated changes in their emotional or behavioral expressions and level of engagement with the PARO robot. METHODS: This was a quasi-experimental study with a repeated measures design. The outcome measures were evaluated at four time-points: before the intervention, week 4, immediately after the intervention, and one month after the PARO intervention. RESULTS: Fifty-two participants were recruited. The age of the participants ranged from 65 to 96 years, with a mean age of 81.81 years (SD = 8.54) in the PARO group and 79.08 years (SD = 7.71) in the control group. Using a mixed between-within subjects' analysis of variance, the results showed that there were significant interaction effects between the groups and time-periods for depression (p < .000), loneliness (p < .000), and engagement (p < .000). CONCLUSIONS: The PARO intervention alleviated depression and loneliness for older adults. Furthermore, the process of engagement with PARO may play an important role in the PARO effects. CLINICAL IMPLICATIONS: A tailored PARO intervention of at least 4 weeks could engender positive psychological benefits for older adults.

Music, heart rate variability, and symptom clusters: a comparative study.

PURPOSE: This study aimed to explore the possible range of change of a single-session music intervention (SMI) on symptom clusters and neurological reactivity for women with breast cancer undergoing chemotherapy. METHODS: A parallel and randomized, controlled study with repeated measures design was used. A total of 100 women with breast cancer were randomly assigned to the SMI or a control group. The outcome measurements of symptom cluster were collected using the Multidimensional Fatigue Symptom Inventory, Pittsburgh Sleep Quality Index, the Hospital Anxiety and Depression Scale, and the neurological reactivity with heart rate variability at four time points: before commencement of the intervention (T0), immediately afterward (T1), 1 week later (T2), and 3 weeks after the intervention (T3). RESULTS: Of the 50 women in each group, 46 in the SMI and 48 in the control group completed the post-test at T3. Multivariate analysis of variance indicated that the SMI group had a medium effect in change of symptom clusters compared to the control group at T2. Moreover, after adjusting for baseline between normal and higher levels of sympathetic tone activity, significant differences existed in fatigue and depression at T2 and sleep disturbance at T3. CONCLUSIONS: A single-session music intervention can be effectively used to reduce symptom clusters for women with breast cancer. Targeting those who have a higher level of sympathetic tone activity is recommended.

A social robot intervention on depression, loneliness, and quality of life for Taiwanese older adults in long-term care.

OBJECTIVES: To investigate the effect of a social robot intervention on depression, loneliness, and quality of life of older adults in long-term care (LTC) and to explore participants' experiences and perceptions after the intervention. DESIGN: A mixed-methods approach consisting of a single group, before and after quasi-experimental design, and individual interview. PARTICIPANTS: Twenty older adults with depression from four LTC facilities in Taiwan were recruited. INTERVENTION: Each participant participated in 8 weeks of observation and 8 weeks of intervention. In the observation stage, participants received usual care or activities without any research intervention. In the intervention stage, each participant was given a Paro (Personal Assistive RobOt) to keep for 24 hours, 7 days a week. MEASUREMENTS: The Geriatric Depression Scale, the UCLA Loneliness Scale Version 3, and the World Health Organization Quality of Life Questionnaire for older adults were administered at four time points. Individual qualitative interviews with thematic analysis followed. RESULTS: A repeated multivariate analysis of variance and Friedman's test showed no significant changes during the observation stage between T1 and T2 for depression and quality of life (p >.5). For the intervention stage, statistically significant changes in decreasing depression and loneliness and improving quality of life over time were identified. Three themes emerged from the interviews: (i) humanizing Paro through referring to personal experiences and engagement; (ii) increased social interaction with other people; and (iii) companionship resulting in improved mental well-being. CONCLUSIONS: There were significant improvements in mental well-being in using Paro. Further research may help us to understand the advantages of using a Paro intervention as depression therapy.

Factors associated with the intention to use adult preventive health services in Taiwan.

OBJECTIVE: This research aimed to examine the factors associated with the intention to use adult preventive health services in Taiwan. DESIGN AND SAMPLE: Using Andersen's behavioral model, we employed a cross-sectional descriptive design to investigate 500 samples from four communities in southern Taiwan. MEASURES: We used a self-reported survey to assess participants' intention to use adult preventive health services, and the predisposing, enabling, and need factors influencing their intention. RESULTS: Intention to use adult preventive health services was more significantly explained by predisposing and enabling factors than by need factors. In addition, a lack of fixed medical facilities (enabling factor) and Taiwanese origin (predisposing factor) were associated with decreased odds of intention to use adult preventive health services. An educational level of high school or below (predisposing factor), higher amounts of exercise (predisposing factor), and lower barriers to use preventive health services (predisposing factor) were associated with increased odds of intention to use adult preventive health services. CONCLUSION: The findings can assist public health nurses in identifying high-risk groups with lower intentions of using adult preventive health services. Additionally, community-based health education program can be developed to increase people's intention to use adult preventive health services.

Zinc Finger-Containing Cellular Transcription Corepressor ZBTB25 Promotes Influenza Virus RNA Transcription and Is a Target for Zinc Ejector Drugs.

Influenza A virus (IAV) replication relies on an intricate interaction between virus and host cells. How the cellular proteins are usurped for IAV replication remains largely obscure. The aim of this study was to search for novel and potential cellular factors that participate in IAV replication. ZBTB25, a transcription repressor of a variety of cellular genes, was identified by an RNA interference (RNAi) genomic library screen. Depletion of ZBTB25 significantly reduced IAV production. Conversely, overexpression of ZBTB25 enhanced it. ZBTB25 interacted with the viral RNA-dependent RNA polymerase (RdRp) protein and modulated its transcription activity. In addition, ZBTB25 also functioned as a viral RNA (vRNA)-binding protein, binding preferentially to the U-rich sequence within the 5' untranslated region (UTR) of vRNA. Both protein-protein and protein-RNA interactions involving ZBTB25 facilitated viral RNA transcription and replication. In addition, ZBTB25 suppressed interferon production, further enhancing viral replication. ZBTB25-associated functions required an intact zinc finger domain and posttranslational SUMO-1 modification of ZBTB25. Furthermore, treatment with disulfiram (a zinc ejector) of ZBTB25-overexpressing cells showed significantly reduced IAV production as a result of reduced RNA synthesis. Our findings indicate that IAV usurps ZBTB25 for IAV RNA synthesis and serves as a novel and potential therapeutic antiviral target.IMPORTANCE IAV-induced seasonal influenza causes severe illness and death in high-risk populations. However, IAV has developed resistance to current antiviral drugs due to its high mutation rate. Therefore, development of drugs targeting cellular factors required for IAV replication is an attractive alternative for IAV therapy. Here, we discovered a cellular protein, ZBTB25, that enhances viral RdRp activity by binding to both viral RdRp and viral RNA to stimulate viral RNA synthesis. A unique feature of ZBTB25 in the regulation of viral replication is its dual transcription functions, namely, promoting viral RNA transcription through binding to the U-rich region of vRNA and suppressing cellular interferon production. ZBTB25 contains a zinc finger domain that is required for RNA-inhibitory activity by chelating zinc ions. Disulfiram treatment disrupts the zinc finger functions, effectively repressing IAV replication. Based on our findings, we demonstrate that ZBTB25 regulates IAV RNA transcription and replication and serves as a promising antiviral target for IAV treatment.

Comparison of group vs self-directed music interventions to reduce chemotherapy-related distress and cognitive appraisal: an exploratory study.

PURPOSE: The purpose of this study was to determine effects of group music intervention and self-directed music intervention on anxiety, depression, and cognitive appraisal among women with breast cancer. METHODS: A quasi-experimental design randomly assigned 60 women undergoing chemotherapy to 3 groups: group music intervention, self-directed music intervention, or a control group. The Hospital Anxiety and Depression Scale and the Mini-Mental Adjustment to Cancer Scale were administered before, after the 8-week interventions, and at 3-month follow-up. RESULTS: Of the 52 women completing the study, results indicated that group music intervention had a significant (p < .01) immediate effect to decrease helplessness/hopelessness and anxious preoccupation and significant effects for reducing anxiety, depression, helplessness/hopelessness, and cognitive avoidance compared to the other two groups at 3-month follow-up. CONCLUSIONS: Group music intervention can be considered an effective supportive care in alleviating the chemotherapy-related distress and enhancing cognition modification of women with breast cancer. Further research is needed to determine the role of cognitive appraisal in the illness trajectory.

Social Robots for Depression in Older Adults: A Systematic Review.

PURPOSE: In recent years, there has been an increase in the number of studies using social robots to improve psychological well-being. This systematic review investigates the effect of social robot interventions for depression in older adults. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) method was used to identify and select existing studies. Nine electronic databases were searched for relevant studies. Methodological quality was assessed using the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument. Screening, data extraction, and synthesis were performed by three reviewers. Inclusion criteria covered original quantitative studies investigating social robots for depression in older adults. FINDINGS: Seven studies were identified-six randomized controlled trials and one comparison study-with all classified as good quality. Social robot interventions consisted of companion, communication, and health-monitoring robots. Three studies presented promising outcomes for reducing depressive symptoms in older adults following social robot interventions, and three studies showed decreased, but nonsignificant, trends in depression scores. CONCLUSIONS: The results highlight the potential of social robot interventions for reducing depression in older adults. However, the evidence is not strong enough to formulate recommendations on clinical effectiveness. CLINICAL RELEVANCE: Social robots are being used with increasing frequency to potentially provide personal support to older adults living in long-term care facilities. Social robots can be used to help alleviate depressive symptoms when used in group activities.

Portable Bladder Ultrasound Reduces Incidence of Urinary Tract Infection and Shortens Hospital Length of Stay in Patients With Acute Ischemic Stroke.

BACKGROUND: Urinary tract infection (UTI) during acute ischemic stroke is associated with a longer hospital length of stay and unfavorable functional outcomes. OBJECTIVE: We investigated the benefits of portable bladder ultrasound (PBU) scanning during acute ischemic stroke. METHODS: We retrospectively reviewed patients with acute ischemic stroke from January 2011 to February 2017. Patients were divided into group 1 (PBU not available) and group 2 (PBU available), before or after the split date, April 9, 2014. Portable bladder ultrasound scanning was conducted by nurses to measure postvoid residual urine volume in patients with impaired consciousness and/or dependent ambulation. RESULTS: In total, 1928 patients were enrolled, of whom 109 (5.7%) had UTI and 901 (46.7%) experienced unfavorable outcomes (modified Rankin scale score ≥ 3). Multivariate analysis revealed that factors that influenced UTI were age of 75 years or older, female gender, initial total National Institutes of Health Stroke Scale (NIHSS) score of 5 or higher, initial NIHSS conscious score of 1 or higher, initial NIHSS leg score of 2 or higher, and urinary catheterization. Factors influencing unfavorable outcomes were similar to those influencing UTI but further comprised UTI. C-statistic for UTI detection was 0.864 for model fitting, including significant factors in logistic regression. Compared with group 1, group 2 had a higher incidence of urinary catheterization (13.1% vs 8.2%), a lower incidence of UTI (4.0% vs 6.9%), and a shorter length of stay (11.9 vs 13.6 days). CONCLUSIONS: Portable bladder ultrasound scanning reduced the incidence of UTI and shortened length of stay. We suggest routine PBU procedures for patients with acute ischemic stroke who fulfill the AGN3 criteria for a high risk of UTI.

Predicting genome terminus sequences of Bacillus cereus-group bacteriophage using next generation sequencing data.

BACKGROUND: Most tailed bacteriophages (phages) feature linear dsDNA genomes. Characterizing novel phages requires an understanding of complete genome sequences, including the definition of genome physical ends. RESULT: We sequenced 48 Bacillus cereus phage isolates and analyzed Next-generation sequencing (NGS) data to resolve the genome configuration of these novel phages. Most assembled contigs featured reads that mapped to both contig ends and formed circularized contigs. Independent assemblies of 31 nearly identical I48-like Bacillus phage isolates allowed us to observe that the assembly programs tended to produce random cleavage on circularized contigs. However, currently available assemblers were not capable of reporting the underlying phage genome configuration from sequence data. To identify the genome configuration of sequenced phage in silico, a terminus prediction method was developed by means of 'neighboring coverage ratios' and 'read edge frequencies' from read alignment files. Termini were confirmed by primer walking and supported by phylogenetic inference of large DNA terminase protein sequences. CONCLUSIONS: The Terminus package using phage NGS data along with the contig circularity could efficiently identify the proximal positions of phage genome terminus. Complete phage genome sequences allow a proposed characterization of the potential packaging mechanisms and more precise genome annotation.

Dynamic association rules for gene expression data analysis.

BACKGROUND: The purpose of gene expression analysis is to look for the association between regulation of gene expression levels and phenotypic variations. This association based on gene expression profile has been used to determine whether the induction/repression of genes correspond to phenotypic variations including cell regulations, clinical diagnoses and drug development. Statistical analyses on microarray data have been developed to resolve gene selection issue. However, these methods do not inform us of causality between genes and phenotypes. In this paper, we propose the dynamic association rule algorithm (DAR algorithm) which helps ones to efficiently select a subset of significant genes for subsequent analysis. The DAR algorithm is based on association rules from market basket analysis in marketing. We first propose a statistical way, based on constructing a one-sided confidence interval and hypothesis testing, to determine if an association rule is meaningful. Based on the proposed statistical method, we then developed the DAR algorithm for gene expression data analysis. The method was applied to analyze four microarray datasets and one Next Generation Sequencing (NGS) dataset: the Mice Apo A1 dataset, the whole genome expression dataset of mouse embryonic stem cells, expression profiling of the bone marrow of Leukemia patients, Microarray Quality Control (MAQC) data set and the RNA-seq dataset of a mouse genomic imprinting study. A comparison of the proposed method with the t-test on the expression profiling of the bone marrow of Leukemia patients was conducted. RESULTS: We developed a statistical way, based on the concept of confidence interval, to determine the minimum support and minimum confidence for mining association relationships among items. With the minimum support and minimum confidence, one can find significant rules in one single step. The DAR algorithm was then developed for gene expression data analysis. Four gene expression datasets showed that the proposed DAR algorithm not only was able to identify a set of differentially expressed genes that largely agreed with that of other methods, but also provided an efficient and accurate way to find influential genes of a disease. CONCLUSIONS: In the paper, the well-established association rule mining technique from marketing has been successfully modified to determine the minimum support and minimum confidence based on the concept of confidence interval and hypothesis testing. It can be applied to gene expression data to mine significant association rules between gene regulation and phenotype. The proposed DAR algorithm provides an efficient way to find influential genes that underlie the phenotypic variance.

Stress, sleep quality and unplanned Caesarean section in pregnant women.

This study examines the relationship among prenatal maternal stress, sleep quality and unplanned Caesarean delivery. For this research, we adopted a prospective survey design and a sample of 200 women in the early stages of labour. The findings were as follows: (i) 11.5% of the participants underwent unplanned Caesarean sections; (ii) based on a Pittsburg Sleep Quality Index split point of 5, approximately 90.5% of the participants experienced poor sleep quality; and (iii) the odds ratio for primiparas undergoing an unplanned Caesarean section was 4.183 times that for multiparas (95% confidence interval (CI) = 1.177 to 14.864), indicating a statistically significant difference. The results also showed that stress was a significant factor related to unplanned Caesarean sections; a 1-point increase on the Pregnancy Stress Rating Scale was associated with a 1.033-fold higher probability of undergoing an unplanned Caesarean section (95% CI = 1.002 to 1.065). Furthermore, prenatal stress was a significant variable that can be used to predict unplanned Caesarean deliveries.

Overexpressed-eIF3I interacted and activated oncogenic Akt1 is a theranostic target in human hepatocellular carcinoma.

UNLABELLED: Eukaryotic translation initiation factor 3 subunit I (eIF3I) with transforming capability is often overexpressed in human hepatocellular carcinoma (HCC) but its oncogenic mechanisms remain unknown. We demonstrate that eIF3I is overexpressed in various cancers along with activated Akt1 phosphorylation and kinase activity in an eIF3I dose-dependent manner. A novel eIF3I and Akt1 protein interaction was identified in HCC cell lines and tissues and was required for eIF3I-mediated activation of Akt1 signaling. Expression of either antisense eIF3I or dominant negative Akt1 mutant suppressed eIF3I-mediated Akt1 oncogenic signaling and various other tumorigenic effects. Oncogenic domain mapping of the eIF3I and Akt1 interaction suggested that the C-terminal eIF3I interacted with the Akt1 kinase domain and conferred the majority of oncogenic functions. In addition, eIF3I interaction with Akt1 prevented PP2A dephosphorylation of Akt1 and resulted in constitutively active Akt1 oncogenic signaling. Importantly, concordant expression of endogenous eIF3I and phospho-Akt1 was detected in HCC cell lines and tissues. Treatment of eIF3I overexpressing HCC cells with the Akt1 specific inhibitor API-2 suppressed eIF3I-mediated tumorigenesis in vitro and in vivo. CONCLUSION: We describe a constitutive Akt1 oncogenic mechanism resulting from interaction of overexpressed eIF3I with Akt1 that prevents PP2A-mediated dephosphorylation. Overexpression of eIF3I in HCC is oncogenic and is a surrogate marker and therapeutic target for treatment with Akt1 inhibitors.

[Nursing care for a lung cancer patient with brain metastasis using the family resiliency model].

This article describes the experience of the author in providing nursing care to a lung cancer patient with brain metastasis who was unable to care for herself. The period of care ran from July 26th to August 7th, 2012. The focus of the article is on the problems of disease adaptation and the coping strategies of the patient and her primary caregivers. The author used the Family Resiliency Model to collect information via physical examination, observation, and interviews. Five major nursing problems were identified in this case: risk of aspiration, self-care deficits, adjustment disorder, caregiver role strain, and family coping ineffectiveness. Based on these problems, the author constructed an individualized care plan to: 1) improve the self-care ability of the patient, 2) enhance the skills of the primary caregiver, 3) recruit the timely assistance of other family members, 4) and reduce the burden of the primary caregiver. The primary goal of this care plan was to promote the quality of life of the patient and her family.

Hepatocellular carcinoma surveillance at 4- vs. 12-month intervals for patients with chronic viral hepatitis: a randomized study in community.

OBJECTIVES: To compare the efficacy of hepatocellular carcinoma (HCC) surveillance at 4- and 12-month intervals in a community for patients with chronic viral hepatitis and thrombocytopenia. METHODS: In 10 townships, adults (≥ 40 years) with platelet ≤ 150 (× 10(9))/l, positive hepatitis B surface antigen, or antibody to hepatitis C virus were invited to this study. These townships were randomized into 4- (group A) and 12-month (group B) interval surveillance groups. Seven hundred and eighty-five and 796 residents met the study criteria in groups A and B. Ultrasonography (US) was the surveillance method. RESULTS: A total of 744 residents (group A: 387; group B: 357) were enrolled. In the study period, HCC was diagnosed in 39 residents (group A: 24; group B: 15). There was no difference in cumulative 3-year HCC incidence between the two groups. The tumors were smaller in group A than in group B, though group A had more patients with tumor ≤ 2 cm (P = 0.003) who were in Barcelona Clinic Liver Cancer (BCLC) very-early stage (P = 0.017) and had undergone curative treatments (P = 0.049). Male gender, cirrhosis, and platelet ≤ 100 (× 10(9))/l were associated factors of HCC occurrence. There was no difference in 4-year overall survival between the two groups. Patients undergoing recommended treatments had better 4-year survival rates. CONCLUSIONS: Compared with 12-month interval, US surveillance at 4-month interval detected more patients with HCC ≤ 2 cm who were in BCLC very-early stage and were fit for curative treatments. Up to 4-year follow-up, however, the overall survival was not different.