bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and Correlates of Mental Health Problems in Canadian Forces Personnel Who Deployed in Support of the Mission in Afghanistan: Findings from Postdeployment Screenings, 2009–2012
Authors: Zamorski Mark A , Rusu Corneliu , Garber Bryan G
Published: July 2017

Objective:

An important minority of military personnel will experience mental health problems after overseas deployments. Our study sought to describe the prevalence and correlates of postdeployment mental health problems in Canadian Forces personnel.

Method:

Subjects were 16 193 personnel who completed postdeployment screening after return from deployment in support of the mission in Afghanistan. Screening involved a detailed questionnaire and a 40-minute, semi-structured interview with a mental health clinician. Mental health problems were assessed using the Patient Health Questionnaire and the Posttraumatic Stress Disorder Checklist—Civilian Version. Logistic regression was used to explore independent risk factors for 1 or more of 6 postdeployment mental health problems.

Results:

Symptoms of 1 or more of 6 mental health problems were seen in 10.2% of people screened; the most prevalent symptoms were those of major depressive disorder (3.2%), minor depression (3.3%), and posttraumatic stress disorder (2.8%). The strongest risk factors for postdeployment mental health problems were past mental health care (adjusted odds ratio [AOR] 2.89) and heavy combat exposure (AOR 2.57 for third tertile, compared with first tertile). These risk groups might be targeted in prevention and control efforts. In contrast to findings from elsewhere, Reservist status, deployment duration, and number of previous deployments had no relation with mental health problems.

Conclusions:

An important minority of personnel will disclose symptoms of mental health problems during postdeployment screening. Differences in risk factors seen in different nations highlight the need for caution in applying the results of research in one population to another.
A Sex-Specific Comparison of Major Depressive Disorder Symptomatology in the Canadian Forces and the General Population
Authors: Erickson Julie , Kinley D Jolene , Bolton James M , Zamorski Mark A , Enns Murray W , Sareen Jitender
Published: July 2017

Objective:

To compare major depressive disorder (MDD) symptomatology within men and women in a large, representative sample of Canadian military personnel and civilians.

Method:

We used the Canadian Community Health Survey: Mental Health and Well-Being (Cycle 1.2 and Canadian Forces Supplement) ( n = 36 984 and n = 8441, respectively) to compare past-year MDD symptomatology among military and civilian women, and military and civilian men. Logistic regression models were used to determine differences in the types of depressive symptoms endorsed in each group.

Results:

Men in the military with MDD were at lower odds than men in the general population to endorse numerous symptoms of depression, such as hopelessness (adjusted odds ratio [AOR] 0.44; 99% CI 0.23 to 0.83) and inability to cope (AOR 0.53; 99% CI 0.31 to 0.92). Military women with MDD were at lower odds of thinking about their death (AOR 0.52; 99% CI 0.32 to 0.86), relative to women with MDD in the general population.

Conclusion:

Different MDD symptomatology among males and females in the military, compared with those in the general population, may reflect selection effects (for example, personality characteristics and patterns of comorbidity) or occupational experiences unique to military personnel. Future research examining the mechanisms behind MDD symptomatology in military personnel and civilians is required.
Competent Psychopharmacology
Authors: Gardner David M
Published: July 2017

There is little doubt that undergraduate and post-graduate training of physicians, pharmacists, and nurses is insufficient to prepare them to use psychotropics safely and effectively, especially in the context of their expanded off-label uses. Therefore, the development of competencies in psychotropic prescribing needs to be approached as a long-term, practice-based learning commitment. Proposed are the abilities and knowledge components necessary for safe and effective use of psychotropics. Typical challenges in prescribing for chronic and recurrent illnesses include highly variable responses and tolerability, drug interactions, and adverse effects that can be serious, irreversible, and even fatal. Prescribing psychotropics is further complicated by negative public and professional reports and growing patient concerns about the quality of care, and questions about the efficacy, safety, and addictive risks of psychotropics. Increased efforts are needed to enhance clinical training and knowledge in psychopharmacology among trainees and practising clinicians, with more comprehensive and sustained attention to the assessment of individual patients, and greater reliance on patient education and collaboration. Improved competence in psychotropic prescribing should lead to more informed, thoughtful, and better-targeted applications as one component of more comprehensive clinical care.
Time Trends in Medically Serious Suicide-Related Behaviours in Boys and Girls
Authors: Rhodes Anne E , Lu Hong , Skinner Robin
Published: July 2017

Objective:

To determine whether emergency department (ED) presentations for suicide-related behaviours (SRBs) in boys and girls were identified as more clinically acute in the ED in the period after the regulatory warnings against prescribing antidepressants and during the global economic recession, and to characterize the medical severity of SRBs among boys and girls to aid surveillance activities.

Method:

Among Ontario boys and girls (aged 12 to 17 years) presenting to the ED with an incident (index) ED SRB event between fiscal years (FYs) 2002 to 2010, we compared the number of high (compared with lower) acuity events in FYs 2005 to 2010 to those in FYs 2002 to 2004. We described the SRB method by its acuity and tested the linearity of varying trends in the SRB method in boys and girls.

Results:

In both boys and girls, high acuity events were 50% greater after FY 2004 than before, regardless of subsequent admission, and most common among boys and girls who self-poisoned. In girls, opposing linear trends before and after FY 2004 were observed in the proportion of self-poisonings and cut (or) pierce SRB methods. Throughout the study period, there was a linear decline in the proportion of boys presenting to the ED with other methods.

Conclusions:

The previously reported increase in hospital admissions after the warnings and during the recession is unlikely artifactual. An equivalent increase in high acuity events was also evident among those not subsequently admitted. The reasons for varying responses in boys and girls by SRB method warrant further study.
Research Experience in Psychiatry Residency Programs across Canada: Current Status
Authors: Shanmugalingam Arany , Ferreria Sharon G , Norman Ross M G , Vasudev Kamini
Published: July 2017

Objective:

To determine the current status of research experience in psychiatry residency programs across Canada.

Method:

Coordinators of Psychiatric Education (COPE) resident representatives from all 17 psychiatry residency programs in Canada were asked to complete a survey regarding research training requirements in their programs.

Results:

Among the 17 COPE representatives, 15 completed the survey, representing 88% of the Canadian medical schools that have a psychiatry residency program. Among the 15 programs, 11 (73%) require residents to conduct a scholarly activity to complete residency. Some of these programs incorporated such a requirement in the past 5 years. Ten respondents (67%) reported availability of official policy and (or) guidelines on resident research requirements. Among the 11 programs that have a research requirement, 10 (91%) require residents to complete 1 scholarly activity; 1 requires completion of 2 scholarly activities. Eight (53%) residency programs reported having a separate research track. All of the programs have a research coordinator and 14 (93%) programs provide protected time to residents for conducting research. The 3 most common types of scholarly activities that qualify for the mandatory research requirement are a full independent project (10 programs), a quality improvement project (8 programs), and assisting in a faculty project (8 programs). Six programs expect their residents to present their final work in a departmental forum. None of the residency programs require publication of residents' final work.

Conclusions:

The current status of the research experience during psychiatry residency in Canada is encouraging but there is heterogeneity across the programs.
Changing Perceptions of Mental Health in Canada
Authors: Patten Scott B , Williams Jeanne V A , Lavorato Dina H , Fiest Kirsten M , Bulloch Andrew G M , Wang JianLi
Published: July 2017

Objective:

Epidemiologic studies typically assess mental health using diagnostic measures or symptom severity measures. However, perceptions are also important. The objective of our study was to evaluate trends in perceived mental health in Canada during the past 20 years using data collected in a series of surveys.

Method:

Perceived mental health status, the stressfulness of most days, and perceived general health, have been repeatedly measured in national surveys. In our study, the resulting frequencies and 95% confidence intervals were calculated. Distress was also assessed in the same surveys with the Kessler 6 Psychological Distress Scale, and analyzed using mean scores and frequencies based on cut-points. Data synthesis used forest plots. Time trends were assessed using random effects meta-regression models.

Results:

No detectable changes in distress were found. Similarly, self-rated general health remained stable. However, over time, Canadians became slightly more likely to report that their mental health was merely fair or poor. Conversely, they have been progressively less likely to perceive that their lives are quite a bit or extremely stressful.

Conclusion:

While these observations are ecological, the 2 trends may be related: distressing emotional experiences may increasingly be interpreted as evidence of a disturbance of mental health rather than a reaction to stressful circumstances. These changing perceptions should not be misinterpreted as an epidemic of poor mental health.
“I Don’t Belong Anymore”: Undocumented Latino Immigrants Encounter Social Services in the United States
Authors: Mallet Marie L. , Calvo Rocío , Waters Mary C.
Published: July 2017

As undocumented Latino immigrants transition into adulthood, they also transition into illegality. They move from a somewhat protected status under which they had access to education and other social benefits, to the more vulnerable category of undocumented adults without access to social rights. How undocumented immigrants’ interactions with social services contribute to the formation of their ethnic identity and feelings of belonging to the United States is the focus of this research. Drawing on qualitative interview data from undocumented adults who grew up in the United States, this article shows that as undocumented children transition into adulthood, they face a new system that forces them to learn how to become an immigrant if they want to remain part of American society.
A Meta-Analysis of School-Based Group Contingency Interventions for Students With Challenging Behavior: An Update
Authors: Maggin Daniel M. , Pustejovsky James E. , Johnson Austin H.
Published: July 2017

Group contingencies are recognized as a potent intervention for addressing challenging student behavior in the classroom, with research reviews supporting the use of this intervention platform going back more than four decades. Over this time period, the field of education has increasingly emphasized the role of research evidence for informing practice, as reflected in the increased use of systematic reviews and meta-analyses. In the current article, we continue this trend by applying recently developed between-case effect size measures and transparent visual analysis procedures to synthesize an up-to-date set of group contingency studies that used single-case designs. Results corroborated recent systematic reviews by indicating that group contingencies are generally effective—particularly for addressing challenging behavior in general education classrooms. However, our review highlights the need for more research on students with disabilities and the need to collect and report information about participants’ functional level.
Tumescent Liposuction under General Anesthesia
Authors: Tobin Howard A.
Published: July 2017

Tumescent liposuction has been recently established as a technique of infiltration of dilute concentrations of lidocaine and adrenalin, which appears to drastically limit the amount of blood loss during liposuction surgery. Previous reports focused on its use under local anesthesia. I have found that it is equally applicable to patients undergoing liposuction surgery under general anesthesia and have also found that the concentration of adrenalin can be reduced from 1: 1,000,000 to 1: 4,000,000 without compromising the hemostatic effects. The technique allows relatively large amounts of fat to be aspirated safely without autologous transfusion.
Adipose Tissue Metabolism: Review, in vitro Studies, and Body Fat Distribution Correlates
Authors: Scarborough Dwight A. , Bisaccia Emil , Cornwell David G. , Whisler Ronald L. , Liu Yiling , Panganamala Rao
Published: July 2017

Adipose tissue metabolism, its regulatory control mechanisms, and its overall relationship to health and disease have been the subject of intense study over the past decade. In this article the metabolic characteristics of adipose tissue are outlined, and the authors' preliminary data from in vitro studies are summarized. Recent findings regarding body fat topography and associated metabolic characteristics are reviewed, with possible implications relating to body contouring surgery.
Advances in Breast Implant Fillers
Authors: Shiffman Melvin A.
Published: July 2017

Introduction:

The moratorium on the use of silicone-gel-filled breast implants in the U.S., Canada, and France has resulted in a flurry of research to find a mammary implant that will replace or surpass the performance of the silicone-gel breast implant and the saline breast implant. The purpose of this review is to briefly present the latest information from the literature on potential breast implant fillers currently under evaluation.

Materials and Methods:

The latest scientific findings on mammary augmentation implants and fillers were reviewed.

Conclusions:

There is still a long way to go before a satisfactory implant filler is found and is approved by the FDA. It is essential that all proposed fillers be researched carefully so that harmful effects are discovered before patients are exposed.
The Role of Parents and Peers in the Transition From University to Work Life
Authors: Buhl Heike M. , Noack Peter , Kracke Baerbel
Published: July 2017

This longitudinal study addresses the role of support given by parents and peers during the transition from university to work life. A sample of 64 German university students in their last year at the university completed scales from the Network of Relationships Inventory regarding general support, namely, instrumental aid and intimacy with mothers, fathers, romantic partners, and friends. Four years later, they assessed domain-specific support when looking for work, namely, joint exploration and instrumental support. Participants perceived receiving both types of support from all significant others. However, joint exploration was more important than instrumental support. They felt especially supported by romantic partners. Women received more support than did men. Both types of domain-specific support were explained by general modes of support assessed 4 years earlier. Whether parents, friends, and partners were perceived as helpful during the transition was explained mainly by joint exploration. Again, support from a partner was seen as especially helpful in contrast to help from parents and friends. The special significance of joint exploration underlines the benefit of counseling at the transition from university to work life.
I Think Immigrants “Kind of Fall Into Two Camps”: Boundary Work by U.S.-Born Community Members in St. Louis, Missouri
Authors: Dorner Lisa M. , Crawford Emily R. , Jennings Joel , Sandoval J. S. Onésimo , Hager Emily
Published: July 2017

To understand how educational policies are created and supported for immigrants and their children, we must explore how community members make sense of broader immigrant/immigration discourses. Guided by theories of “boundary work,” grounded analyses of 27 interviews with U.S.-born residents in metropolitan St. Louis (a community with diverse and increasing immigration) revealed conflicting and ambivalent discourses. Respondents’ opinions shifted as they conceptualized affiliations and borders—real and symbolic—between themselves and foreign-born individuals. The discussion will address how the “hardening” or “blurring” of such boundaries can affect the development and support of educational policies for immigrants and refugees.
The politics of love in contemporary China: Cosmopolitanism and competing masculinities in Best Time
Authors: Guo Shaohua
Published: July 2017

Since the new millennium, the television industry in China has witnessed a flourishing of television series addressing the aspirations, struggles and gender expectations of the urban middle class. Nevertheless, with few exceptions, little scholarly attention has been devoted to the televisual construction of masculine ideals in the contemporary era. Taking as a case study Best Time (最美的时光), one of the most popular idol dramas of 2013, this article fills a lacuna in current scholarship and addresses the televisual construction of cosmopolitan masculinities by focusing on the tension between two prominent social groups: overseas returnees and indigenous talents. Through analysis of the construction of competing masculinities in Best Time, this article argues that this drama is as much about an undertone of national rejuvenation, and the desire for China’s rise and global dominance, as it is about unrequited love. In pursuing this argument, a critical reading of a youth idol drama opens new avenues for understanding cosmopolitanism through the lenses of gender dynamics and nationalism.
Study on the pitch curve with minimal rotary inertia for the noncircular gears
Authors: Zhang Xin , Fan Shouwen
Published: July 2017

Aimed at the high load and slow response of the noncircular gears design, a general mathematical model for designing the pitch curve with minimal rotary inertia of the noncircular gear is proposed by resorting to kinematics principle and calculus of variations. To achieve the closure design, the constraint conditions and smoothness characteristics of N-lobed noncircular gear pitch curve with minimal rotary inertia are established and calculated analytically. In addition, the unified design method of the conjugate pitch curves with minimal rotary inertia for the noncircular gears is given in this paper. Unclosed and closed N-lobed conjugate pitch curves that satisfy the desired transmission requirements can be easily solved by using the proposed method, and each lobe has identical profile to ensure the periodical motion of the pitch curves. Numerical examples are implemented in computer and demonstrate the feasibility of the above method.
Study and results of an onboard brake monitoring system for freight wagons
Authors: Aimar M , Somà A
Published: July 2017

This paper presents the background study, development, and testing of a monitoring system for an intermodal freight wagon. The prototype of the onboard unit, developed by the research group of Railway Engineering of Politecnico di Torino, was installed and tested on an intermodal freight wagon owned by the company Ambrogio Trasporti S.p.a. as part of the project ITS Cluster Italy 2020. Significant advances have been made in the field of freight train monitoring. In recent years, many companies have presented specific devices with the aim of monitoring the operating conditions of goods wagons. The developed prototype was tested on a real track. The main vehicle parameters monitored during the tests were the temperature of brake blocks, the operating pressure of the brake system, and the acceleration of the vehicle. The measurements allowed the team to verify the effectiveness and reliability of the monitoring system in harsh conditions. A significant amount of the measured data was then used to validate a first energetic model that is useful for the subsequent development of monitoring and diagnostic algorithms.
Efficient airplane arrival scheduling using a set partitioning-based branch-and-price method
Authors: Song Jae-Hoon , Choi Han-Lim
Published: July 2017

This article presents an exact algorithm that is combined with a heuristic method to find the optimal solution for an airplane landing problem. For a given set of airplanes and runways, the objective is to minimize the accumulated deviations from the target landing time of the airplanes. A cost associated with landing either earlier or later than the target landing time is incurred for each airplane within its predetermined time window. In order to manage this type of large-scale optimization problem, a set partitioning formulation that results in a mixed integer linear program is proposed. One key contribution of this article is the development of a branch-and-price methodology, in which the column generation method is integrated with the branch-and-bound method in order to find the optimal integer solution. In addition to the exact algorithm, a simple heuristic method is also presented to tighten the solution space. Numerical experiments are undertaken for the proposed algorithm in order to confirm its effectiveness using public data from the OR-Library. As an application in the real-world situation of airplane landing, air traffic data from Incheon International Airport is employed to assure the efficiency of the proposed algorithm.
Global Increases in Individualism
Authors: Santos Henri C. , Varnum Michael E. W. , Grossmann Igor
Published: July 2017

Individualism appears to have increased over the past several decades, yet most research documenting this shift has been limited to the study of a handful of highly developed countries. Is the world becoming more individualist as a whole? If so, why? To answer these questions, we examined 51 years of data on individualist practices and values across 78 countries. Our findings suggest that individualism is indeed rising in most of the societies we tested. Despite dramatic shifts toward greater individualism around the world, however, cultural differences remain sizable. Moreover, cultural differences are primarily linked to changes in socioeconomic development, and to a lesser extent to shifts in pathogen prevalence and disaster frequency.
Two Equals One: Two Human Actions During Social Interaction Are Grouped as One Unit in Working Memory
Authors: Ding Xiaowei , Gao Zaifeng , Shen Mowei
Published: July 2017

Every day, people perceive other people performing interactive actions. Retaining these actions of human agents in working memory (WM) plays a pivotal role in a normal social life. However, whether the semantic knowledge embedded in the interactive actions has a pervasive impact on the storage of the actions in WM remains unknown. In the current study, we investigated two opposing hypotheses: (a) that WM stores the interactions individually (the individual-storage hypothesis) and (b) that WM stores the interactions as chunks (the chunk-storage hypothesis). We required participants to memorize a set of individual actions while ignoring the underlying social interactions. We found that although the social-interaction aspect was task irrelevant, the interactive actions were stored in WM as chunks that were not affected by memory load (Experiments 1 and 2); however, inverting the human actions vertically abolished this chunking effect (Experiment 3). These results suggest that WM automatically and efficiently used semantic knowledge about interactive actions to store them and support the chunk-storage hypothesis.
Gununa peacemaking
Authors: Brigg Morgan , Memmott Paul , Venables Philip , Zondag Berry
Published: July 2017

Informal conflict management implicitly claims to value cultural difference and to be able to mediate relations between cultural minorities and states. This article considers this claim in challenging circumstances borne of settler-colonialism by examining the cultural politics of the establishment of a conflict resolution programme in an Australian Aboriginal community. In addition to settler-colonial maligning of Aboriginal capacities to manage conflict, the Gununa community has in recent decades faced the severe attenuation of customary processes and escalating uncontrolled violence. Nonetheless, the Mornington Island Restorative Justice Project involved a spontaneous appropriation of mediation as a customary initiative and an accompanying implicit negotiation between the customary sociolegal order of Mornington Islanders and that of the liberal settler-state. Analysis of these circumstances and relations leads us to argue that informalism can support cultural difference and mediate relations with the state, although it cannot be relied upon to transform the accompanying asymmetric relationship. Nonetheless, informalism may sustain and contribute to the possibilities for transformative change by improving delivery of justice services and through recognition of Indigenous capacities and approaches to sociopolitical order.
The Performance of Thai Manufacturing SMEs: Data Envelopment Analysis (DEA) Approach
Authors: Charoenrat Teerawat , Harvie Charles
Published: July 2017

This study applies a data envelopment analysis (DEA) approach and a two-limit Tobit model to measure the technical efficiency of Thai manufacturing small and medium enterprises (SMEs) and examine firm-specific factors contributing to it by using firm-level industrial censuses data in 1997 and 2007. The empirical results reveal that the overall average technical efficiency is relatively low, which can potentially reduce their output contribution. Empirical results also indicate that firm size, firm age, skilled labour, location, type of manufacturing ownerships, cooperatives, foreign investment and exports are important firm-specific factors contributing to the technical efficiency of Thai manufacturing SMEs. Therefore, specific policies are required to improve the technical efficiency of SMEs and these include easier access to financial services, credit facilities, equity in terms of the political operation, educational system, extensive infrastructural development and technological upgrading, marketing and management.
MicroRNA-25 suppresses proliferation, migration, and invasion of osteosarcoma by targeting SOX4
Authors: Chen Bingpeng , Liu Jingjing , Qu Ji , Song Yang , Li Yuxiang , Pan Su
Published: July 2017

Altered expression of the miR-25 has been implicated in many human malignant progression as oncogene or tumor suppressor. However, the precise role of miR-25 in osteosarcoma progression remains largely unclear. This study aimed to investigate the role and underlying mechanism of miR-25 in osteosarcoma. In this study, we demonstrated that miR-25 was significantly downregulated in osteosarcoma cell lines and tissues and that lower miR-25 was associated with advanced tumor–node–metastasis stage and lymph node metastasis. Then, we found that introduction of miR-25 significantly suppressed the proliferation, colony formation, migration, and invasion of osteosarcoma cells in vitro and retarded tumor growth in vivo. Further studies indicated that the epithelial–mesenchymal transition–related transcription factor, SOX4 (SRY-related high-mobility group box 4), was a direct target gene of miR-25, evidenced by bioinformatics analysis predicted and luciferase reporter assay. Furthermore, miR-25 could decrease the expression of SOX4 levels and inhibited epithelial–mesenchymal transition process. The levels of miR-25 were inversely correlated with those of SOX4 expression in osteosarcoma tissues. SOX4 overexpression rescued miR-25-induced suppression of proliferation, migration, and invasion of osteosarcoma cells. Taken together, these results suggest that miR-25 functions as a tumor suppressor in the progression of osteosarcoma by repressing SOX4.
MicroRNA-21 versus microRNA-34: Lung cancer promoting and inhibitory microRNAs analysed in silico and in vitro and their clinical impact
Authors: Kunz Meik , Göttlich Claudia , Walles Thorsten , Nietzer Sarah , Dandekar Gudrun , Dandekar Thomas
Published: July 2017

MicroRNAs are well-known strong RNA regulators modulating whole functional units in complex signaling networks. Regarding clinical application, they have potential as biomarkers for prognosis, diagnosis, and therapy. In this review, we focus on two microRNAs centrally involved in lung cancer progression. MicroRNA-21 promotes and microRNA-34 inhibits cancer progression. We elucidate here involved pathways and imbed these antagonistic microRNAs in a network of interactions, stressing their cancer microRNA biology, followed by experimental and bioinformatics analysis of such microRNAs and their targets. This background is then illuminated from a clinical perspective on microRNA-21 and microRNA-34 as general examples for the complex microRNA biology in lung cancer and its diagnostic value. Moreover, we discuss the immense potential that microRNAs such as microRNA-21 and microRNA-34 imply by their broad regulatory effects. These should be explored for novel therapeutic strategies in the clinic.
Cordycepin induces apoptosis in human bladder cancer cells via activation of A3 adenosine receptors
Authors: Cao Hong-Li , Liu Zi-Jin , Chang Zheng
Published: July 2017

Bladder cancer is a neoplasm originated from bladder epithelial cells. The therapy for bladder cancer is so far not satisfactory. In this study, we examined the effects of Cordyceps militaris hot water extracts containing cordycepin on human bladder cells. Cordyceps militaris hot water extracts containing cordycepin was used to treat human T24 bladder carcinoma cells, and we found that Cordyceps militaris hot water extracts containing cordycepin decreased T24 cell survival in a dose-dependent manner, which was seemingly mediated by activation of A3 adenosine receptor and the subsequent inactivation of Akt pathways, resulting in increases in cleaved Caspase-3 and apoptosis. Overexpression of A3 adenosine receptor in T24 cells mimicked the effects of Cordyceps militaris hot water extracts, while A3 adenosine receptor depletion abolished the effects of Cordyceps militaris hot water extracts containing cordycepin. Together, these data suggest that Cordyceps militaris hot water extracts containing cordycepin may be a promising treatment for bladder cancer via A3 adenosine receptor activation.
TMEM88, CCL14 and CLEC3B as prognostic biomarkers for prognosis and palindromia of human hepatocellular carcinoma
Authors: Zhang Xin , Wan Jin-Xiang , Ke Zun-Ping , Wang Feng , Chai Hai-Xia , Liu Jia-Qiang
Published: July 2017

Hepatocellular carcinoma is one of the most mortal and prevalent cancers with increasing incidence worldwide. Elucidating genetic driver genes for prognosis and palindromia of hepatocellular carcinoma helps managing clinical decisions for patients. In this study, the high-throughput RNA sequencing data on platform IlluminaHiSeq of hepatocellular carcinoma were downloaded from The Cancer Genome Atlas with 330 primary hepatocellular carcinoma patient samples. Stable key genes with differential expressions were identified with which Kaplan–Meier survival analysis was performed using Cox proportional hazards test in R language. Driver genes influencing the prognosis of this disease were determined using clustering analysis. Functional analysis of driver genes was performed by literature search and Gene Set Enrichment Analysis. Finally, the selected driver genes were verified using external dataset GSE40873. A total of 5781 stable key genes were identified, including 156 genes definitely related to prognoses of hepatocellular carcinoma. Based on the significant key genes, samples were grouped into five clusters which were further integrated into high- and low-risk classes based on clinical features. TMEM88, CCL14, and CLEC3B were selected as driver genes which clustered high-/low-risk patients successfully (generally, p = 0.0005124445). Finally, survival analysis of the high-/low-risk samples from external database illustrated significant difference with p value 0.0198. In conclusion, TMEM88, CCL14, and CLEC3B genes were stable and available in predicting the survival and palindromia time of hepatocellular carcinoma. These genes could function as potential prognostic genes contributing to improve patients’ outcomes and survival.
Impact of tumor architecture on disease recurrence and cancer-specific mortality of upper tract urothelial carcinoma treated with radical nephroureterectomy
Authors: Fan Bo , Hu Bin , Yuan Qingmin , Wen Shuang , Liu Tianqing , Bai Shanshan , Qi Xiaofeng , Wang Xin , Yang Deyong , Sun Xiuzhen , Song Xishuang
Published: July 2017

Upper tract urinary carcinoma (UTUC) is a relatively uncommon but aggressive disease. Recent publications have assessed the prognostic significance of tumor architecture in UTUC, but there is still controversy regarding the significance and importance of tumor architecture on disease recurrence. We retrospectively reviewed the medical records of 101 patients with clinical UTUC who had undergone surgery. Univariate and multivariate analyses were conducted to identify factors associated with disease recurrence and cancer-specific mortality. As our single center study and the limited sample size may influence the clinical significance, we further quantitatively combined the results with those of existing published literature through a meta-analysis compiled from searching several databases. At a median follow-up of 41.3 months, 25 patients experienced disease recurrence. Spearman’s correlation analysis showed that tumor architecture was found to be positively correlated with the tumor location and the histological grade. Kaplan-Meier curves showed that patients with sessile tumor architecture had significantly poor recurrence free survival (RFS) and cancer specific survival (CSS). Furthermore, multivariate analysis suggested that tumor architecture was independent prognostic factors for RFS (Hazard ratio, HR = 2.648) and CSS (HR = 2.072) in UTUC patients. A meta-analysis of investigating tumor architecture and its effects on UTUC prognosis was conducted. After searching PubMed, Medline, Embase, Cochrane Library and Scopus databases, 17 articles met the eligibility criteria for this analysis. The eligible studies included a total of 14,368 patients and combined results showed that sessile tumor architecture was associated with both disease recurrence with a pooled HR estimate of 1.454 and cancer-specific mortality with a pooled HR estimate of 1.416. Tumor architecture is an independent predictor for disease recurrence after radical nephroureterectomy for UTUC. Therefore, closer surveillance is necessary, especially in patients with sessile tumor architecture.
Remodeling of extracellular matrix of the lamina propria in the uninvolved human rectal mucosa 10 and 20 cm away from the malignant tumor
Authors: Despotović Sanja Z , Milićević Novica M , Milošević Dragoslav P , Despotović Nebojša , Erceg Predrag , Svorcan Petar , Schumacher Udo , Ullrich Sebastian , Mihajlović Gordana , Kalem Dragan , Marković Srđan , Lalić Ivana M , Krmpot Aleksandar J , Rabasović Mihailo D , Pantelić Dejan V , Jovanić Svetlana Z , Rösch Thomas , Milićević Živana
Published: July 2017

In recent years, it has been demonstrated that malignancy arises and advances through the molecular interplay between tumor cells and non-malignant elements of the tumor stroma, that is, fibroblasts and extracellular matrix. However, in contrast to the mounting evidence about the role of tumor stroma in the genesis and progression of the malignant disease, there are very few data regarding the uninvolved stromal tissue in the remote surrounding of the tumor. Using the objective morphometric approach in patients with adenocarcinoma, we demonstrate the remodeling of extracellular matrix of the lamina propria in the uninvolved rectal mucosa 10 and 20 cm away from the neoplasm. We show that the representation of basic extracellular matrix constituents (reticular and collagen fibers and ground substance) is decreased. Also, the diameter of empty spaces that appear within the extracellular matrix of the lamina propria is increased. These spaces do not represent the blood or lymphatic vessel elements. Very likely, they reflect the development of tissue edema in the remote, uninvolved lamina propria of the mucosa in patients with the malignant tumor of the rectum. We hypothesize that the remodeling of extracellular matrix in lamina propria of the rectal mucosa may increase its stiffness, modulating the mechano-signal transduction, and thus promote the progression of the malignant disease.
Evaluation of epigenetic inactivation of vascular endothelial growth factor receptors in head and neck squamous cell carcinoma
Authors: Misawa Yuki , Misawa Kiyoshi , Kawasaki Hideya , Imai Atsushi , Mochizuki Daiki , Ishikawa Ryuji , Endo Shiori , Mima Masato , Kanazawa Takeharu , Iwashita Toshihide , Mineta Hiroyuki
Published: July 2017

The aim of this study was to determine the methylation status of the genes encoding the vascular endothelial growth factor receptors and to evaluate the usefulness of VEGFR methylation as a prognostic indicator in head and neck squamous cell carcinoma. VEGFR messenger RNA expression and promoter methylation were examined in a panel of cell lines via quantitative reverse transcription and methylation-specific polymerase chain reaction, respectively. Promoter methylation was compared with clinical characteristics in 128 head and neck squamous cell carcinoma samples. The normalized methylation values for the VEGFR1, VEGFR2 and VEGFR3 promoters tended to be higher in the tumour cell lines than in normal tonsil samples, whereas amounts of VEGFR1, VEGFR2 and VEGFR3 messenger RNA were significantly higher. Methylation of the VEGFR1 promoter (p = 0.003; 66/128 head and neck squamous cell carcinoma samples, 52%) and VEGFR3 promoter (p = 0.043; 53/128 head and neck squamous cell carcinoma samples, 41%) significantly correlated with recurrence, whereas methylation of the VEGFR2 promoter significantly correlated with lymph node metastasis (p = 0.046; 47/128 head and neck squamous cell carcinoma samples, 37%). Concurrent methylation of the VEGFR1 and VEGFR3 promoters significantly correlated with reduced disease-free survival (log-rank test, p = 0.009). In a multivariate logistic regression analysis, methylation of the VEGFR1, VEGFR3 and both the VEGFR1 and VEGFR3 promoters independently predicted recurrence (odds ratios and 95% confidence intervals: 3.19, 1.51–6.75 (p = 0.002); 2.24, 1.06–4.76 (p = 0.035); and 2.56, 1.09–6.05 (p = 0.032), respectively). Methylation of the VEGFR promoters predicts poor prognosis in head and neck squamous cell carcinoma patients.
Cervical cancer cell–derived angiopoietins promote tumor progression
Authors: Yang Ping , Chen Na , Yang Dongyun , Crane Janet , Huang Bangxing , Dong Ruiqing , Yi Xiaoqing , Guo Jing , Cai Jing , Wang Zehua
Published: July 2017

Metastatic or recurrent cervical cancer has limited treatment options and a high rate of mortality. Although anti-vascular endothelial growth factor drugs have shown great promise as a therapeutic target for treatment of advanced cervical cancer, drug resistance and class-specific side effects negate long-term benefits. The identification of alternative anti-angiogenic factors will be critical for future drug development for advanced or recurrent cervical cancer. In this study, we found that angiopoietins and Tie receptors were highly expressed in cervical cancer cells. Tie-2 expression in tumor cells predicted poorer prognosis. Wound closure assay and Transwell assay showed that upregulated or downregulated Ang-1 and Ang-2 expression promoted or reduced cervical cancer cell lines migration and invasion, respectively. In subcutaneous xenograft models of cervical cancer, downregulation of Ang-1 and Ang-2 attenuated tumor growth. The expression of vimentin and endomucin and microvessel density were all significantly decreased in the siAng-1 group and siAng-2 group relative to the infection control group. Our data support that dual inhibition of Ang-1 and Ang-2 may be an alternative target for anti-angiogenic adjuvant therapy in advanced or recurrent cervical squamous cell cancer.
Long non-coding RNA SPRY4-IT1 promotes proliferation and invasion by acting as a ceRNA of miR-101-3p in colorectal cancer cells
Authors: Jin Jianguang , Chu Zhijie , Ma Pengfei , Meng Yuanpu , Yang Yanhui
Published: July 2017

Long non-coding RNAs are associated with a spectrum of biological processes such as gene regulation on transcriptional and post-transcriptional levels. Increasing evidence indicates that SPRY4-IT1 plays an important role in carcinogenesis, and the mechanisms whereby SPRY4-IT1 induces colorectal carcinoma progression remain largely unknown. The aim of this study is to evaluate the expression and function of SPRY4-IT1 in colorectal carcinoma. In this study, we analyzed SPRY4-IT1 expression levels in a series of colorectal carcinoma patients by quantitative reverse transcription polymerase chain reaction. Knockdown of SPRY4-IT1 by RNA interference was performed to explore its roles in cell proliferation, migration, and invasion. Our results found that SPRY4-IT1 was upregulated in human primary colorectal carcinoma tissues. Knockdown of SPRY4-IT1 inhibited colorectal carcinoma cell proliferation, migration, and invasion. Moreover, we confirmed that the expression of epithelial–mesenchymal transition–related genes was modulated through alteration of SPRY4-IT1 expression. SPRY4-IT1 could negatively regulate the expression of miR-101-3p in colorectal carcinoma cells. The bioinformatics prediction revealed putative miR-101-3p binding sites within SPRY4-IT1 transcripts. Above all, knockdown of SPRY4-IT1 could represent a rational therapeutic strategy for colorectal carcinoma.
HPV16 E6/E7 upregulates HIF-2α and VEGF by inhibiting LKB1 in lung cancer cells
Authors: Shao Jian-Shuang , Sun Jian , Wang Shiyu , Chung Katherine , Du Jin Tong , Wang Jason , Qiu Xue-Shan , Wang En-Hua , Wu Guang-Ping
Published: July 2017

Long-term persistent infection of HPV16 E6/E7 is frequently associated with lung cancers, especially in non-smokers and in Asians. However, molecular mechanisms of HPV16 E6/E7 induction of lung cancer are not fully understood. Using bi-directional genetic manipulation and four well-established lung cancer cell lines, we showed HPV16 E6/E7 downregulated expression of liver kinase B1 at both protein and messenger RNA levels; liver kinase B1 downregulated hypoxia-inducible factor 2α at protein level but not at messenger RNA level, and hypoxia-inducible factor 2α upregulated vascular endothelial growth factor at both protein and messenger RNA levels. This is the first study to show hypoxia-inducible factor 2α as a downstream effector of liver kinase B1 in lung cancer cells. Our results indicate that HPV16 E6/E7 indirectly upregulated the expression of vascular endothelial growth factor by inhibition of liver kinase B1 expression and upregulation of hypoxia-inducible factor 2α expression, thus propose a human papillomavirus–liver kinase B1–hypoxia-inducible factor 2α–vascular endothelial growth factor axis for the tumorigenesis of lung cancer. Our study also provides new evidence to support the critical role of liver kinase B1 in the pathogenesis of human papillomavirus–related lung cancer and suggests novel therapeutic targets.
The long non-coding RNA MALAT1 promotes the migration and invasion of hepatocellular carcinoma by sponging miR-204 and releasing SIRT1
Authors: Hou Zhouhua , Xu Xuwen , Zhou Ledu , Fu Xiaoyu , Tao Shuhui , Zhou Jiebin , Tan Deming , Liu Shuiping
Published: July 2017

Increasing evidence supports the significance of long non-coding RNA in cancer development. Several recent studies suggest the oncogenic activity of long non-coding RNA metastasis–associated lung adenocarcinoma transcript 1 (MALAT1) in hepatocellular carcinoma. In this study, we explored the molecular mechanisms by which MALAT1 modulates hepatocellular carcinoma biological behaviors. We found that microRNA-204 was significantly downregulated in sh-MALAT1 HepG2 cell and 15 hepatocellular carcinoma tissues by quantitative real-time polymerase chain reaction analysis. Through bioinformatic screening, luciferase reporter assay, RNA-binding protein immunoprecipitation, and RNA pull-down assay, we identified microRNA-204 as a potential interacting partner for MALAT1. Functionally, wound-healing and transwell assays revealed that microRNA-204 significantly inhibited the migration and invasion of hepatocellular carcinoma cells. Notably, sirtuin 1 was recognized as a direct downstream target of microRNA-204 in HepG2 cells. Moreover, si-SIRT1 significantly inhibited cell invasion and migration process. These data elucidated, by sponging and competitive binding to microRNA-204, MALAT1 releases the suppression on sirtuin 1, which in turn promotes hepatocellular carcinoma migration and invasion. This study reveals a novel mechanism by which MALAT1 stimulates hepatocellular carcinoma progression and justifies targeting metastasis–associated lung adenocarcinoma transcript 1 as a potential therapy for hepatocellular carcinoma.
MicroRNA-139-5p inhibits bladder cancer proliferation and self-renewal by targeting the Bmi1 oncogene
Authors: Luo Hongbo , Yang Rui , Li Chun , Tong Yongqing , Fan Lingling , Liu Xiuheng , Xu Chuanrui
Published: July 2017

MiR-139-5p has been reported to be overexpressed in many types of cancers, but its role in bladder cancer has not been elucidated yet. Here, we report that miR-139-5p functions as a tumor suppressor in bladder cancer and inhibits the cancer stem cell self-renewal by targeting Bmi1 directly. We found that miR-139-5p expression was significantly downregulated in the bladder cancer specimens compared with that in adjacent normal tissues. In vitro, restoration of miR-139-5p expression significantly inhibited the proliferation of bladder cancer cells. Mechanism analysis revealed that miR-139-5p could decrease Bmi1 protein levels by binding to the 3′ untranslated region of Bmi1 messenger RNA. Stem cell–related proteins such as c-MYC, NANOG, OCT4, and KLF4 and signaling pathways such as Wnt signaling were suppressed by restoration of miR-139-5p in bladder cancer cells. In addition, miR-139-5p expression also blocked self-renewal of bladder cancer stem cells by inhibiting Bmi1. In summary, our study supports that miR-139-5p acts as a tumor suppressor in bladder cancer development and suppresses cancer stem cell property of bladder cancer. Our study also suggests that miR-139-5p has the potential to be used as a therapeutic molecule for bladder cancer treatment.