Immunological role and prognostic value of the SKA family in pan-cancer analysis.

Background: The spindle and kinetochore associated (SKA) complex, which plays important roles in proper chromosome segregation during mitosis by maintaining the stabilization of kinetochore-spindle microtubule attachment during mitosis, has recently been reported to exert regulatory effects on the initiation and progression of various human cancer types. Nevertheless, the prognostic significance and immune infiltration of the SKA family across cancers have not been well elucidated. Methods: Using data from three large public datasets, including The Cancer Genome Atlas, Genotype-Tissue Expression, and Gene Expression Omnibus databases, a novel scoring system (termed the SKA score) was developed to quantify the SKA family level across cancers. We then evaluated the prognostic impact of the SKA score on survival and assessed the effect of the SKA score on immunotherapy at the pan-cancer level using multiomics bioinformatic analyses. The correlation of the SKA score and the tumor microenvironment (TME) was also explored in depth. Potential small molecular compounds and chemotherapeutic agents were assessed by CTRP and GDSC analyses. Immunohistochemistry was performed to verify the expression of the SKA family genes. Results: Our results demonstrated a close correlation between the SKA score and tumor development and prognosis in multiple cancers. The SKA score was positively related to cell cycle pathways and DNA replication across cancers, such as E2F targets, the G2M checkpoint, MYC targets V1/V2, mitotic spindles and DNA repair. Additionally, the SKA score was negatively related to the infiltration of various immune cells with antitumor effects in the TME. In addition, the potential value of the SKA score was identified to predict immunotherapy response for melanoma and bladder cancer. We also demonstrated a correlation between SKA1/2/3 and the response to drug treatment across cancers and the promising potential of the SKA complex and its genes as therapeutic targets in cancer. Immunohistochemistry demonstrated that the expression differences of SKA1/2/3 were significant between the breast cancer group and the paracancerous group. Conclusion: The SKA score plays a critical role in 33 cancer types and is highly related to tumor prognosis. Patients with elevated SKA scores have a clear immunosuppressive TME. The SKA score may serve as a predictor for patients receiving anti-PD-1/L1 therapy.

Integrated analysis of mRNA and microRNA expression profiles in hepatopancreas of Litopenaeus vannamei under acute exposure to MC-LR.

Intensive shrimp farming is often threatened by microcystins Hepatopancreas is the primary target organ of MCs in shrimp. To investigate the response of hepatopancreas to acute MC-LR exposure, the expression profiles of RNA-seq and miRNA-seq in the hepatopancreas of L. vannamei were determined, and data integration analysis was performed at 72 h after MC-LR injection. The expression of 5 DEGs and three DEMs were detected by Quantitative PCR (qPCR). The results showed that the cumulative mortality rate of shrimp in MC-LR treatment group was 41.1%. A total of 1229 differentially expressed genes (844 up- and 385 down-regulated) and 86 differentially expressed miRNAs (40 up- and 46 down-regulated) were identified after MC-LR exposure. Functional analysis indicated that DEGs is mainly involved in the oxidative activity process in molecular functional categories, and proteasome was the most enriched KEGG pathway for mRNAs profile. According to the functional annotation of target genes of DEMs, protein binding was the most important term in the GO category, and protein processing in endoplasmic reticulum (ER) was the most enriched KEGG pathway. The regulatory network of miRNAs and DEGs involved in the pathway related to protein degradation in endoplasmic reticulum was constructed, and miR-181-5p regulated many genes in this pathway. The results of qPCR showed that there were significant differences in the expression of five DEGs and three DEMs, which might play an important role in the toxicity and hepatopancreas detoxification of MC-LR in shrimp. The results revealed that MC-LR exposure affected the degradation pathway of misfolded protein in ER of L. vannamei hepatopancreas, and miR-181-5p might play an important role in the effect of MC-LR on the degradation pathway of misfolded protein.

Practitioners' perspectives on family-based intervention for illicit drug-using adolescents in Taiwan: a qualitative study.

BACKGROUND: Drug-related psychiatric comorbidity or death among adolescents has grown to become a public health threat in Taiwan. In an atmosphere of abstinence, few alternatives or rehabilitative options for troubled young people have caused many juveniles to be driven away from home and placed in closed institutions. The intersectionality of illegal substance use, deviant behaviours, and criminal offences among adjudicated adolescents is a challenge for the development of adolescent users' harm reduction strategies. In addition, the relationships among the adolescents, their families, and practitioners might be undermined by coercive and mandatory court measures. As developing a harm reduction approach includes minimizing the negative effects on not only adolescents and also their families, this study aims to explore Taiwanese practitioners' perspectives of family-based programmes for drug-using adolescents. METHODS: This study adopted a qualitative approach. Through face-to-face interviews and a focus group, accounts were collected from 28 key informants working in youth delinquency. The interviews were transcribed for analysis using qualitative analysis software, namely NVivo10. RESULTS: Practitioners tend to refer to an "adolescent-centred model" when describing their work with drug-using young people. From the frontline practitioners' descriptions, the families of those youth needing treatment services are often vulnerable and disadvantaged. These families are seldom onboard because of low readiness and scarce resources. Although a legal framework is in place, resources, workforce, and programmes to engage and involve parents in the intervention are lacking. Despite the obstacles, practitioners have utilized a variety of strategies to obtain limited success, such as parent meetings, resources referrals, parent counselling, court support, voluntary parenting courses, illicit substance information sharing, and home visits. Practitioners also pointed out that therapeutic interventions are more effective than coercive or mandatory interventions for adolescents and also for their families. CONCLUSIONS: Since most practitioners have an adolescent-centred work principle, their work with parents falls into professional-centred or family-allied work models. It is therefore suggested that resources be reallocated to involve parent counselling and intense treatment instead of mandatory parental education.

Cultivation of Intrapreneurship: A Framework and Challenges.

Intrapreneurship has drawn research attention over the past decades considering its crucial role in innovation, organizational performance, and employee career planning. Intrapreneurial research based on various concepts also emerges. In spite of the increasing concern in the field, contributions in the field are fragmented. Particularly, intrapreneurship research is still lacking an integrated framework based on which, enablers and important facilitating mechanisms can be identified to enhance intrapreneurship. To close the above research gap, the study develops a holistic intrapreneurial framework. Specifically, the study first examines intrapreneurship in relation to other prominent concepts (i.e., innovation, entrepreneurship, and sustainability). This study then identifies enablers of intrapreneurship at both individual and organizational level. Notably, extant research largely examines intrapreneurship either at the organizational or individual level, and concentrates in corporate entrepreneurship or individual intrapreneurial employees. Research providing a holistic perspective on enablers for intrapreneurship is rare. The study further integrates these intrapreneurial enablers with facilitating mechanisms and proposes a framework of intrapreneurship. The framework makes it possible to clearly identify pivotal antecedents to intrapreneurship based on various theoretical lenses and analytical levels applied. Finally, the study addresses a list of managerial and technological challenges arising from the above framework and suggests future research agenda.

Using Machine Learning Approaches to Predict Target Gene Expression in Rice T-DNA Insertional Mutants.

To change the expression of the flanking genes by inserting T-DNA into the genome is commonly used in rice functional gene research. However, whether the expression of a gene of interest is enhanced must be validated experimentally. Consequently, to improve the efficiency of screening activated genes, we established a model to predict gene expression in T-DNA mutants through machine learning methods. We gathered experimental datasets consisting of gene expression data in T-DNA mutants and captured the PROMOTER and MIDDLE sequences for encoding. In first-layer models, support vector machine (SVM) models were constructed with nine features consisting of information about biological function and local and global sequences. Feature encoding based on the PROMOTER sequence was weighted by logistic regression. The second-layer models integrated 16 first-layer models with minimum redundancy maximum relevance (mRMR) feature selection and the LADTree algorithm, which were selected from nine feature selection methods and 65 classified methods, respectively. The accuracy of the final two-layer machine learning model, referred to as TIMgo, was 99.3% based on fivefold cross-validation, and 85.6% based on independent testing. We discovered that the information within the local sequence had a greater contribution than the global sequence with respect to classification. TIMgo had a good predictive ability for target genes within 20 kb from the 35S enhancer. Based on the analysis of significant sequences, the G-box regulatory sequence may also play an important role in the activation mechanism of the 35S enhancer.

Dynamics of Leaf-Litter Biomass, Nutrient Resorption Efficiency and Decomposition in a Moso Bamboo Forest After Strip Clearcutting.

Strip clearcutting can significantly reduce the harvesting costs of moso bamboo forests. Although bamboo is characterized by rapid accumulation of biomass, it is still a concern that this management method may reduce long-term productivity. Nutrient cycling has long been considered essential for forests to maintain high primary productivity. However, nutrient cycling of bamboo forests after strip cutting has not been previously reported. We conducted a strip clearcutting experiment and surveyed the litter dynamics for 1 year. We assessed changes in litter nutrients in response to the cutting and calculated the nutrient resorption efficiency and litter decomposition rate to evaluate the effect on nutrient use efficiency and nutrient return. Our results showed that strip cutting had no significant effect on litter production and nutrient return in the moso bamboo forest (p > 0.05). However, annual litter biomass and nutrient return in reserved belts (RB) were significantly higher than those in the control (CK) (p < 0.05). P and K resorption efficiencies in RB were significantly higher than in CK during certain periods of bamboo growth (p < 0.05). We also observed that the annual decay constant of CK was significantly higher than that of plots that were strip clearcut (SC) (p < 0.05). Our results suggest that strip cutting does not affect nutrient use efficiency or storage in the short term.

GasPhos: Protein Phosphorylation Site Prediction Using a New Feature Selection Approach with a GA-Aided Ant Colony System.

Protein phosphorylation is one of the most important post-translational modifications, and many biological processes are related to phosphorylation, such as DNA repair, transcriptional regulation and signal transduction and, therefore, abnormal regulation of phosphorylation usually causes diseases. If we can accurately predict human phosphorylation sites, this could help to solve human diseases. Therefore, we developed a kinase-specific phosphorylation prediction system, GasPhos, and proposed a new feature selection approach, called Gas, based on the ant colony system and a genetic algorithm and used performance evaluation strategies focused on different kinases to choose the best learning model. Gas uses the mean decrease Gini index (MDGI) as a heuristic value for path selection and adopts binary transformation strategies and new state transition rules. GasPhos can predict phosphorylation sites for six kinases and showed better performance than other phosphorylation prediction tools. The disease-related phosphorylated proteins that were predicted with GasPhos are also discussed. Finally, Gas can be applied to other issues that require feature selection, which could help to improve prediction performance. GasPhos is available at http://predictor.nchu.edu.tw/GasPhos.

QUATgo: Protein quaternary structural attributes predicted by two-stage machine learning approaches with heterogeneous feature encoding.

Many proteins exist in natures as oligomers with various quaternary structural attributes rather than as single chains. Predicting these attributes is an essential task in computational biology for the advancement of proteomics. However, the existing methods do not consider the integration of heterogeneous coding and the accuracy of subunit categories with limited data. To this end, we proposed a tool that can predict more than 12 subunit protein oligomers, QUATgo. Meanwhile, three kinds of sequence coding were used, including dipeptide composition, which was used for the first time to predict protein quaternary structural attributes, and protein half-life characteristics, and we modified the coding method of the functional domain composition proposed by predecessors to solve the problem of large feature vectors. QUATgo solves the problem of insufficient data for a single subunit using a two-stage architecture and uses 10-fold cross-validation to test the predictive accuracy of the classifier. QUATgo has 49.0% cross-validation accuracy and 31.1% independent test accuracy. In the case study, the accuracy of QUATgo can reach 61.5% for predicting the quaternary structure of influenza virus hemagglutinin proteins. Finally, QUATgo is freely accessible to the public as a web server via the site http://predictor.nchu.edu.tw/QUATgo.

Unmet needs and service satisfaction of victim support for the direct and indirect victims of serious violence: Results from a cross-sectional survey in Taiwan.

Victim support services, in mature societies, aim to help victims recover after suffering a traumatic event. The effectiveness of victim support has traditionally been evaluated through rates of service utilization and incidence of psychopathology such as posttraumatic stress disorder. The current study, instead, inquires into service users' unmet needs and satisfaction, and identifies factors that mediate such subjective measures, using data from a national cross-sectional survey on victims and surviving families of violent crime in Taiwan in 2011. The results reveal: 1) a gap between available and expected services, and 2) a correlation between service utilization and satisfaction, both consistent with previous studies. In addition, the current study identifies unsatisfied service users: They are homicidally bereaved, live with their spouse, suffer from post-crime financial distress and are still waiting for a court verdict on the incident. Victim support that helps victims heal through tailored services incorporating relationship counseling is proposed.

The trafficking of women and girls in Taiwan: characteristics of victims, perpetrators, and forms of exploitation.

BACKGROUND: Prior to the passing of 2009 Human Trafficking Prevention Act (HTPA), human trafficking was underestimated in Taiwan. In the past, domestic trafficking in women and girls often targeted vulnerable groups such as young girls from poor families or minority groups. Since the 1990s, an increasing flow of immigrant women, mainly from Vietnam and Indonesia and some from China, into Taiwan has created a new group of Human Trafficking victims. The current study intends to identify, describe, and categorize reported and prosecuted human trafficking cases involving women and girls according to the HTPA in Taiwan. METHODS: Using the court proceedings of prosecuted trafficking in women and girls cases under Taiwan's HTPA from all 21 districts in Taiwan from 2009 to 2012 under the title keyword of 'Human Trafficking', this current study aims to categorize different patterns of existing trafficking in women and girls in Taiwan. The analysis is based on 37 court cases, involving 195 victimized women and girls and 118 perpetrators. RESULTS: This study identifies six forms of Human Trafficking victims according to their country of origin, vulnerability status, and means of transport. This study found that women and girls suffer from both labor and sexual exploitation, from mainly domestic male perpetrators. While sexual exploitation is more evenly distributed among citizens and immigrants and affects both adults and minors, labor exploitation seems to be an exclusive phenomenon among women immigrant workers in the data. CONCLUSIONS: Human Trafficking cases in Taiwan share many of the similarities of Human Trafficking in other regions, which are highly associated with gender inequality and gender-based vulnerability.

Sanction changes and drunk-driving injuries/deaths in Taiwan.

Driving under the influence (DUI) is one of the major causes of traffic accidents in Taiwan. About 5% of injuries involve DUI, and nearly 20% of deaths are due to alcohol-related crashes. During early 2006 to the end of 2014, the authorities in Taiwan increased the severity of fine and jail penalties for DUI offenders three times. At the same time, the monthly drunk-driving injures decreased nearly 40% and the monthly alcohol-related traffic death dropped more than 80%. In this paper, we examine the effects of sanction changes on the reduction of drunk-driving casualties during this period. We find that drunk-driving injuries and deaths significantly dropped after the statutory changes. The reduction was immediate following all sanction changes that raised the maximum fines or jail terms of DUI offenders. Policies that increased the maximum jail terms of DUI offenders seem to have a better gradual effect on the reduction of alcohol-related traffic casualties. Although increased sanctions are found to be effective in reducing drunk-driving casualties, we need more future research to examine the policy-to-perception and the policy-to-behavior links.

Identifying risk factors for household burdens of road traffic fatalities: regression results from a cross-sectional survey in Taiwan.

BACKGROUND: Road traffic fatalities (RTF) are among the top ten causes of deaths in the world. The risk factors for RTF fatal victims have been extensively characterized, but studies of household burden of RTF have been very few in number. Accordingly, this article investigates post-crash impacts on RTF victims' family members, including the adverse impacts of lost income, occupational disruption, unfavorable family dynamics, and residential relocation. METHODS: Survey data from 1291 RTF family members interviewed in Taiwan in 2012 provide the evidence of impact used in this article. Twelve variables related to the family member's socio-demographic background were used to predict the scope of the adverse impact of a fatal crash in regression models developed for this analysis. RESULTS: RTF victims' spouses with relatively low personal incomes and strong dependence upon the crash victims were found to be most likely to experience a marked decrease in post- crash quality of life. RTF victims' family members who lived with few other adult cohabitants and had more juvenile dependents and were emotionally dependent on the victims were found to be quite likely to experience post- crash setbacks in occupational stability. RTF victims' family members who were emotionally dependent on the victims were found to be more likely to experience major family life disruptions. The younger the RTF victims' family members, and the more years since the crash, the higher the likelihood of residential relocation taking place. CONCLUSIONS: The results noted help identify those RTF victims' families that will most likely be adversely affected by the crash. The true societal costs of RTF crashes should include the adversities suffered by the fatal crash victims' families. Social welfare policies, mental health support, and timely supplemental resources should be made available to those surviving families most at risk of major life disruptions.