bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic investigation on railway vehicle considering the dynamic effect from the axle box bearings
Authors: Li Tao , Sun Wei , Meng Zhichao , Huo Junzhou , Dong Jianghui , Wang Liping
Published: April 2019

The nonlinear load of the axle box bearing and the spatially coupled relationship of vehicles have seldom been considered in the dynamic modeling of vehicle–track systems in recent years. Therefore, based on the time-varying nonlinear contact load of an axle box bearing, a vehicle spatially coupled dynamic model is established. Subsequently, the vehicle–track spatially coupled dynamic model is established by the dynamic coupled relationship between the wheel and rail. Finally, the vehicle wheelset testbed is set up to verify the correctness of the theoretical model. Experimental results show that (1) the vibration of an axle box has a strong nonlinear coupled relationship. The axle box vertical amplitude aroused by lateral alternating load is approximately 0.108 mm, which was approximately 22.2% of the lateral vibration and (2) the lateral displacement and acceleration errors of axle box between the simulation and experiment are about 5.7% and 6.9%, respectively, which validates the theoretical model. The vehicle–track spatially coupled dynamic model accurately reflects the vibration characteristics of locomotives under track irregularity and provides theoretical support for the design of key components, such as axle box bearings.
Cell-free DNA testing: future applications in gastroenterology and hepatology
Authors: Zandvakili Inuk , Lazaridis Konstantinos N.
Published: April 2019

The application of next-generation sequencing in clinical practice is increasing as accuracy and interpretation have improved and the cost continues to decline rapidly. Cell-free DNA is a unique source for next-generation sequencing that could change routine clinical practice in gastroenterology and hepatology. Testing of cell-free DNA in blood and fecal samples is an easy, rapid, and noninvasive method to assess for premalignant, malignant, metabolic, infectious, inflammatory, and autoimmune gastrointestinal and liver diseases. In this review, we describe cell-free DNA technologies, current applications of cell-free DNA testing, and proposed cell-free DNA targets for gastrointestinal and hepatic diseases, with a specific focus on malignancy. In addition, we provide commentary on how cell-free DNA can be integrated into clinical practice and help guide diagnosis, prognosis, disease management, and therapeutic response.
Hand hygiene practices in the context of Ebola virus disease: A cross-sectional survey of Lagos residents
Authors: Akinyinka Modupe R , Bakare Omowunmi Q , Oluwole Esther O , Odugbemi Babatunde A
Published: April 2019

Background:

The Ebola virus disease outbreak that ravaged parts of West Africa has been described as the most severe acute public health emergency seen in modern times. Hand washing was promoted among other measures for infection prevention.

Objective:

This study assessed the awareness of Ebola virus disease and hand-washing practices among Lagos residents, southwest Nigeria.

Methods:

A descriptive cross-sectional study was used. A total of 1982 respondents aged 18 ⩾ years were selected using a multi stage sampling technique. An interviewer-administered, pre-tested questionnaire was used for data collection between August and November 2015. Data were analysed using the Statistical Package for Social Sciences (SPSS) version 22, with level of significance set at 0.05.

Results:

Almost all (97.3%) respondents were aware of Ebola virus disease, with over half of respondents having heard about it from television. A majority of 1890 (95.4%) respondents were aware of the importance of hand washing in disease prevention. Similarly, high proportions of respondents were aware they should wash their hands after an outing, toilet use, touching pets, before and after meals, while 1628 (82.1%) of respondents knew to wash their hands after a hand shake. However, less than half of respondents (38.8%) always washed their hands after handshakes.

Discussion:

A majority of respondents surveyed were aware of Ebola virus disease and hand washing, but the practice of hand washing, which is key in prevention of infection, lagged behind the knowledge of the respondents.
First-line afatinib for the treatment of EGFR mutation-positive non-small-cell lung cancer in the ‘real-world’ clinical setting
Authors: Park Keunchil , Wan-Teck Lim Darren , Okamoto Isamu , Yang James Chih-Hsin
Published: April 2019

Afatinib is an ErbB family blocker that is approved for the treatment of epidermal growth factor receptor ( EGFR) mutation-positive non-small-cell lung cancer (NSCLC). Pivotal randomized clinical studies demonstrated that afatinib significantly prolonged progression-free survival compared with platinum-based chemotherapy (LUX-Lung 3, LUX-Lung 6), and with gefitinib (LUX-Lung 7), with manageable side effects. However, these results were derived from controlled studies conducted in selected patients and are not necessarily representative of real-world use of afatinib. To gain a broader understanding of the effectiveness and safety of first-line afatinib, we have undertaken a literature review of real-world studies that have assessed its use in a variety of patient populations. We focused on patients with uncommon EGFR mutations, brain metastases, or those of advanced age, as these patients are often excluded from clinical studies but are regularly seen in routine clinical practice. The available real-world studies suggest that afatinib has clinical activity, and is tolerable, in diverse patient populations in an everyday clinical practice setting. Moreover, consistent with LUX-Lung 7, several real-world comparative studies indicate that afatinib might confer better efficacy than first-generation EGFR tyrosine kinase inhibitors. Tolerability-guided dose adjustment, undertaken in 21–68% of patients in clinical practice, did not appear to reduce the efficacy of afatinib. Taken together, these findings provide further support for the use of afatinib as a treatment option in patients with EGFR mutation-positive NSCLC.
tPA for Acute Ischemic Stroke and Its Controversies: A Review
Authors: Dewar Brian , Shamy Michel
Published: April 2019

Background and Purpose:

Although neurologists consider intravenous tissue plasminogen activator (tPA) to be standard of care in the treatment of patients with acute ischemic stroke, its use remains contentious within the broader medical community, and particularly among emergency physicians. Why might this be? We provide a historical context to this ongoing controversy by reviewing how neurologists have conceptualized the acute stroke and its treatment, with the aim of bridging this gap.

Methods:

Based on historical sources in the Mackie Family History of Neuroscience Collection at the University of Calgary, as well as online resources, we trace the evolution of the concept of the “acute stroke,” which has come to mean a stroke that is potentially treatable with tPA. We frame this conceptualization in relation to historical “building blocks” in anatomy, pathology, and physiology. We then use these building blocks to explain why neurologists understand tPA to be effective and why emergency physicians often do not.

Results and Conclusions:

Arguments against the use of tPA reiterate 20-year-old concerns about its efficacy and safety. We believe these persistent concerns can be framed as a lack of understanding of the “building blocks” upon which neurologists’ conception of tPA is built. Our view suggests that the way forward to bridge the gap between neurology and other disciplines is not to conduct more trials but to offer a shared conceptualization of the trials already completed and of the intellectual tradition from which they emerged.
Unfit by Accident: Third-Party Perception of Parental Fitness Based on Childbearing Intention
Authors: Huang Julie Y.
Published: April 2019

Prior research has examined the impact of unintended birth on parent and child welfare. The present studies examine another potential consequence: namely, how third-party observers react to information about parenthood intention. We examine whether the act of having intended (or not) to become a parent affects people’s impressions of (1) what type of caregiver the (un)intended parent will be, (2) the type of relationship the (un)intended parent will have with the child, and (3) potential outcomes for that family. Studies 1 and 2 demonstrate that people award less custody to accidental mothers and fathers because lack of intention during birth is perceived as decreasing parental quality and closeness between parent and child. Study 3 tests potential moderators of this effect including parenthood status and controllability, highlighting the potential negative consequences of this phenomenon for families in child custody disputes where third-party judgments are especially likely to bear weight.
Cognitive Biases and Religious Belief: A Path Model Replication in the Czech Republic and Slovakia With a Focus on Anthropomorphism
Authors: Willard Aiyana K. , Cingl Lubomír , Norenzayan Ara
Published: April 2019

We examined cognitive biases that underlie individual differences in supernatural beliefs in nationally representative samples from the Czech Republic and Slovakia (total N = 2,022). These countries were chosen because of their differing levels of religious belief despite their cultural similarity. Replicating a previous study with North American samples, we found that anthropomorphism was unrelated to belief in God but was consistently related to paranormal beliefs. Living in a highly religious area was related to a lower tendency to anthropomorphize. We examined this relationship further to find that anthropomorphism was related to belief in God for nonreligious participants, was inversely related to belief in God among religious Slovaks, and not related for religious Czechs. These findings suggest that anthropomorphism predicts belief in God for people who are unaffiliated, but this relationship disappears or is reversed for religious believers participating in a Christian religious tradition.
A Growth Mind-Set Intervention Improves Interest but Not Academic Performance in the Field of Computer Science
Authors: Burnette Jeni L. , Hoyt Crystal L. , Russell V. Michelle , Lawson Barry , Dweck Carol S. , Finkel Eli
Published: April 2019

We investigated whether a growth mindset intervention could be leveraged to promote performance and interest in computer science, through what mechanisms it might do so, and whether effects were stronger for women than for men. In particular, we explored whether the growth mindset intervention improved academic performance and career interest by increasing intrinsic value. We developed and tested a scalable, online, 4-session growth mindset intervention at 7 universities, across 16 introductory computer science classes ( N = 491). The intervention did not have a significant total effect on academic performance, although it indirectly improved grades via value. Additionally, the intervention, relative to the control, improved interest in the field and value also mediated this effect. Counter to expectations, the intervention worked equally well for women and men. Theoretical and practical applications are discussed.
Virtual worlds and money laundering under EU law: The inadequacy of the existing legal framework and the challenges of regulation
Authors: Karapatakis Andreas
Published: April 2019

The technological advancements and the rise of online gaming have given birth to a ‘new’ crime, that is, the crime of money laundering through virtual worlds with the use of gaming currency. However, the current European anti-money laundering (AML) regime is incapable of addressing it. The unique environment from virtual worlds renders the traditional notions and definitions about money laundering obsolete and requires from the European Union legislator to take steps towards a more technologized idea of money in order to fight this crime. Nevertheless, the effort for a more contemporary approach of money laundering, and the insertion of gaming currency, in the AML regime is inextricably linked to the comprehension of the present threat from virtual worlds.
Heterogeneous lightweight configuration for protection against 7.62 × 39 mm bullet impact
Authors: Ahmed Khurshid , Malik Abdul Qadeer , Ahmad Iram Raza
Published: April 2019

Configuration of a heterogeneous lightweight material is investigated numerically and experimentally, for protection against 7.62 × 39 mm mild steel core bullet impact. The configuration consists of alumina (Al2O3) tile followed by fiber glass and polyurethane foam, all covered with kev-epoxy layer. Numerical simulations were performed using ANSYS AUTODYN. The 10-mm thick alumina completely disrupts the impacting bullet through blunting and erosion. The fiber glass and polyurethane foam disperse and absorb the propagation of shock wave, respectively. The kev-epoxy cladding seizes any scattering of brittle alumina fragments. The average impact velocity of the bullet was measured to be 710 m/s using high-speed camera. A 10-mm depth of depression spread over a wider area of 3.92 sq in of torso was recorded in blunt force trauma test, which was well within the European, German, and British standards that allow a 20–25 mm backface signature. Due to these characteristics it can be employed as body armor, vehicle armor, and for the safety and security of other critical infrastructures against this bullet and fragment impact. The residual mushroom-shaped bullet and its length of 9.3 mm in numerical simulation is in close agreement with the measured value of the 8.0 mm recovered bullet size and shape.
Brachytherapy for the urologist: A multidisciplinary team update for 2019
Authors: Teixeira Helen , Kang Myungkuk , Lees Kathryn , Beesley Sharon , Edwards Albert , Henderson Alastair
Published: April 2019

Brachytherapy is a well-established treatment for localised prostate cancer. Urologists are often tasked with discussing all available treatment options with the newly diagnosed patient. Unlike radical prostatectomy and external beam radiotherapy, knowledge of brachytherapy may be limited. The aim of this article is to provide an up-to-date guide on patient selection, modern brachytherapy techniques and the management of side effects, such that the core urologist can be more confident in both discussing initial treatment options and the long-term management of brachytherapy patients.

Level of Evidence: Level 5 - review article
IT Governance and Firm Performance: Empirical Study From Saudi Arabia
Authors: Hamdan Allam , Khamis Reem , Anasweh Mohammed , Al-Hashimi Mukhtar , Razzaque Anjum
Published: April 2019

This study provides additional evidence on information technology (IT) governance and its relationship to firm performance in emerging markets. It aims primarily to determine the level of IT governance in Saudi Arabian companies; it also aims at examining the impact of IT governance on the firm performance. The study target sample is 131 companies taken from 20 sectors of the Saudi financial market; during the year 2017. The researchers have used the IT-related backgrounds of the members of the board of directors as an indicator of IT governance. The researchers have also used another group of corporate governance indicators in addition to a set of control variables. The performance of the companies has been referred to as the operational performance which is represented as Return on Assets (ROA) and the financial performance as the Return on Equity (ROE). The descriptive results have been shocking. The study has shown a sharp decline in IT governance in Saudi companies; only 15% of companies have members of the board of directors with IT-related backgrounds, and the IT governance is not adopted or used in many important sectors. However, the regression analysis shows that there is a positive impact on IT governance only on the operational performance of Saudi companies. The results of this study provide a significant indicator of IT governance in Saudi companies. These results can be also used to develop the corporate governance code to focus more on IT governance.
Collaboration for Innovation: An Evidence from Tokyo
Authors: Wahyuni Sari , Onodera Kenji , Wahyuningsih
Published: April 2019

In many literature on innovation, it has been proven that the success of innovation is highly influenced by interorganizational collaboration. The purpose of this case is to provide a complete case study on how academic-business-community-government (ABCG) plus bank partnership can be nurtured to create innovation. To develop successful innovation that could provide hallo economy impact, a systematic strategy development is needed with the support of strong partnership between ABCG and banks. This study uses qualitative approach (direct observation) by taking a case study of Technology Advanced Metropolitan Area (TAMA) in Japan who has successfully developed Greater Tokyo Initiative (GTI). Result of this study shows that to develop a successful cluster, there is a need of systematic cluster strategy with the help of ABCG and bank partnership. This strategy should include cultivation of key persons for local industrial vitalization, analysis for new industries, any kind of supports for planning industrial vitalization plan, supports for collaboration with other areas and also overseas marketing. TAMA is a comprehensive example of ABCG collaboration that not only develop regional network so that some projects can run smoothly but also create collaboration with other cluster in Japan and in the world to contribute to global innovations to strengthen their network.
A Review of Empirical Research on Global Talent Management
Authors: Anlesinya Alex , Dartey-Baah Kwasi , Amponsah-Tawiah Kwesi
Published: April 2019

Global talent management as an academic field is regarded as a multi-disciplinary bridge field, which has recently emerged from the strategic international human resource management (HRM) and talent management fields as a critical strategic issue for multinational firms. While some literature reviews have been conducted on the topic, there is no systematic review of drivers, outcomes and challenges in empirical global talent management research. This study therefore provides a rigorous systematic review of empirical global talent management research from 2008 to 2017. The evidence reveals that global talent management can enhance multinational companies’ global mobility outcomes, employer attractiveness, competitiveness and performance. However, challenges, such as huge financial costs, high rate of turnover among global talents, localization difficulties, corporate culture, and adjustment problems, of expatriate spouses can undermine the effectiveness of global talent management practices and programmes. Furthermore, the findings indicate that the qualitative approach and cross-sectional design have dominated empirical research on the topic while only few studies have performed multi-level analysis. The findings urge stakeholders to adopt a more holistic and well-informed view while designing and implementing global talent management initiatives either as researchers or practitioners. It also implies that despite the substantial interest in global talent management, the field is still under-explored or under-researched. The study makes contribution by providing the first systematic review of empirical global talent management research.
The Textbook Didn’t Mention That: An Intercultural Experiential Exercise in Business Communication
Authors: Luck Susan L. , Swartz Stephanie
Published: April 2019

Although many global MBA programs teach intercultural communication, what happens when the method for teaching that concept becomes mostly experiential? To answer that question, the authors took two very similar classes, both composed of working adults, a Business Communications course in Germany and a Managerial Communications course in the United States, and joined the students into a project that spread over several weeks and had a purposely vague deliverable. While the students believed that the policies and presentations were the most important aspect of the project, the actual aim of this exercise was for them to learn about intercultural communication by doing it. Based on weekly debriefs and a final debrief, group presentations, and individual papers, we concluded that students had increased their understanding of intercultural communication far beyond what they would have gained by merely studying intercultural theory.
Managing non-family talent: Evidence from German-speaking regions
Authors: Harsch Katharina , Festing Marion
Published: April 2019

Family businesses dominate the corporate world but there is much we don’t know about them. Managing non-family talent is one under-researched area which we explore here, using a context-specific analysis on multiple levels, including qualitative data from interviews with family business owners and non-family talents in strategic family business positions in Germany, Austria and German-speaking Switzerland. Based on stewardship theory and our empirical results, we suggest a framework that explains the particular facets of talent management in this context, characterised by the emotional attachment of the family and involvement in the business. Our findings show that primarily the values and attitudes of families shape the specific family business talent management approach, which is embedded in the particularities of the family business culture at the meso level and in region-specific macro-level factors.
Reduced Salience and Enhanced Central Executive Connectivity Following PTSD Treatment
Authors: Abdallah Chadi G. , Averill Christopher L. , Ramage Amy E. , Averill Lynnette A. , Alkin Evelyn , Nemati Samaneh , Krystal John H. , Roache John D. , A. Resick Patricia , Young-McCaughan Stacey , Peterson Alan L. , Fox Peter ,   the STRONG STAR Consortium
Published: April 2019

Background

In soldiers with posttraumatic stress disorder, symptom provocation was found to induce increased connectivity within the salience network, as measured by functional magnetic resonance imaging and global brain connectivity with global signal regression (GBCr). However, it is unknown whether these GBCr disturbances would normalize following effective posttraumatic stress disorder treatment.

Methods

Sixty-nine US Army soldiers with (n = 42) and without posttraumatic stress disorder (n = 27) completed functional magnetic resonance imaging at rest and during symptom provocation using subject-specific script imagery. Then, participants with posttraumatic stress disorder received six weeks (12 sessions) of group cognitive processing therapy or present-centered therapy. At week 8, all participants repeated the functional magnetic resonance imaging scans. The primary analysis used a region-of-interest approach to determine the effect of treatment on salience GBCr. A secondary analysis was conducted to explore the pattern of GBCr alterations posttreatment in posttraumatic stress disorder participants compared to controls.

Results

Over the treatment period, present-centered therapy significantly reduced salience GBCr ( p = .02). Compared to controls, salience GBCr was high pretreatment (present-centered therapy, p = .01; cognitive processing therapy, p = .03) and normalized post-present-centered therapy ( p = .53) but not postcognitive processing therapy ( p = .006). Whole-brain secondary analysis found high GBCr within the central executive network in posttraumatic stress disorder participants compared to controls. Post hoc exploratory analyses showed significant increases in executive GBCr following cognitive processing therapy treatment ( p = .01).

Conclusion

The results support previous models relating cognitive processing therapy to central executive network and enhanced cognitive control while unraveling a previously unknown neurobiological mechanism of present-centered therapy treatment, demonstrating treatment-specific reduction in salience connectivity during trauma recollection.
Physical Activity, Exercise, and Musculoskeletal Disorders in Sonographers
Authors: McDonald Maureen , Salisbury Helen
Published: April 2019

Stretching and exercise are recommended to prevent work-related musculoskeletal disorders (WRMSD) in sonographers, but evidence is lacking. The purpose of this study was to identify sonographers’ physical activity levels and types and frequency of exercise performed regularly. This quantitative descriptive study used a minimally adapted long-form version of the International Physical Activity Questionnaire, distributed to Society of Diagnostic Medical Sonography members. Consistent with prior research, over 80% of 530 participants scanned in pain or had a WRMSD. A majority (85.6%) reported a high level of physical activity from moderate work and domestic-related activities, with a median of 5 hours daily spent sitting. While 69.1% walked or hiked at least one to three times a week, stretching and strength exercises were not as prevalent. Cumulative effects of everyday activities may increase WRMSD risk. Improving muscular fitness and taking time for muscle recovery might help sonographers avoid or reduce WRMSD pain. Implementing and applying preventative WRMSD strategies may need stakeholder support.
Mutations in the zebrafish hmgcs1 gene reveal a novel function for isoprenoids during red blood cell development
Authors: Hernandez Jose A. , Castro Victoria L. , Reyes-Nava Nayeli , Montes Laura P. , Quintana Anita M.
Published: April 2019

Erythropoiesis is the process by which new red blood cells (RBCs) are formed and defects in this process can lead to anemia or thalassemia. The GATA1 transcription factor is an established mediator of RBC development. However, the upstream mechanisms that regulate the expression of GATA1 are not completely characterized. Cholesterol is 1 potential upstream mediator of GATA1 expression because previously published studies suggest that defects in cholesterol synthesis disrupt RBC differentiation. Here we characterize RBC development in a zebrafish harboring a single missense mutation in the hmgcs1 gene (Vu57 allele). hmgcs1 encodes the first enzyme in the cholesterol synthesis pathway and mutation of hmgcs1 inhibits cholesterol synthesis. We analyzed the number of RBCs in hmgcs1 mutants and their wild-type siblings. Mutation of hmgcs1 resulted in a decrease in the number of mature RBCs, which coincides with reduced gata1a expression. We combined these experiments with pharmacological inhibition and confirmed that cholesterol and isoprenoid synthesis are essential for RBC differentiation, but that gata1a expression is isoprenoid dependent. Collectively, our results reveal 2 novel upstream regulators of RBC development and suggest that appropriate cholesterol homeostasis is critical for primitive erythropoiesis.
Evaluation of a re-useable bronchoscopy biosimulator with ventilated lungs
Authors: Garner Justin L. , Garner Stefan D. , Hardie Robin J. , Molyneaux Philip L. , Singh Suveer , Kemp Samuel V. , Shah Pallav L.
Published: April 2019

Background

Restrictions on respiratory trainee time and access to procedures reduce the opportunities to acquire necessary skills in bronchoscopy. Simulation, not subject to such impediments, is a useful supplementary aid to teaching bronchoscopic techniques in a safe environment but there is a limited choice of simulators that are sufficiently realistic and not prohibitively expensive. This study evaluated a low-cost device that simulates an intubated and ventilated patient, employing re-useable, inflatable, BioFlex-preserved, porcine lungs.

Methods

26 bronchoscopists, trainee and experienced, after using the bronchoscopy biosimulator, completed a questionnaire using a five-point Likert scale comparing its performance with that of the computerised CAE AccuTouch.

Results

Participants were largely positive about their experience (mean score of 4.76). The bronchoscopy biosimulator was found to be realistic (mean score 4.64), easy to use (mean score 4.88), and helpful in learning to perform a variety of diagnostic and therapeutic procedures (mean score 4.85). Importantly, the bronchoscopy biosimulator compared favourably to the computer simulator (mean score 4.84).

Conclusions

These data support the concept of the bronchoscopy biosimulator as an acceptable model with which to supplement the experience of bronchoscopic procedures.
Evaluation of unmet clinical needs in prophylaxis and treatment of venous thromboembolism in high-risk patient groups: cancer and critically ill
Authors: Brenner Benjamin , Hull Russell , Arya Roopen , Beyer-Westendorf Jan , Douketis James , Elalamy Ismail , Imberti Davide , Zhai Zhenguo
Published: April 2019

Background

Clinical practice shows that venous thromboembolism (VTE) presents a substantial burden in medical patients, and awareness and advocacy for its primary and secondary prevention remains inadequate. Specific patient populations, such as those with cancer and the critically ill, show elevated risk for VTE, bleeding or both, and significant gaps in VTE prophylaxis and treatment exist in these groups.

Objective

To present current expert insights and evidence on the unmet needs in thromboprophylaxis, and on the treatment of VTE in two high-risk patient groups: patients with cancer and the critically ill.

Methodology

To identify specific unmet needs in the management of VTE, a methodology was designed and implemented that assessed gaps in prophylaxis and treatment of VTE through interviews with 44 experts in the field of thrombosis and haemostasis, and through a review of current guidelines and seminal studies to substantiate the insights provided by the experts. The research findings were then analysed, discussed and consolidated by a multidisciplinary group of experts.

Results

The gap analysis methodology identified shortcomings in the VTE risk assessment tools, patient stratification approaches for prophylaxis, and the suboptimal use of anticoagulants for primary prophylaxis and treatment.

Conclusions

Specifically, patients with cancer need better VTE risk assessment tools to tailor primary thromboprophylaxis to tumour types and disease stages, and the potential for drug–drug interactions needs to be considered. In critically ill patients, unfractionated heparin is not advised as a first-line treatment option, low-molecular weight heparins remain the first choice for prophylaxis in critically ill and cancer patients due to their safety and efficacy profile, and the strength of evidence is increasing for direct oral anticoagulants as a treatment option over low-molecular-weight heparins.

Herein we present novel insights and consolidated evidence collected from experts, clinical practice guidelines and original studies on the unmet needs in thromboprophylaxis, and on the treatment of VTE in patients with cancer and the critically ill.
RETRACTED ARTICLE: A positive feedback loop consisting of C12orf59/NF-κB/CDH11 promotes gastric cancer invasion and metastasis
Authors: Zhang Jia-Xing , He Wei-Ling , Feng Zi-Hao , Chen Dong-Liang , Gao Ying , He Ying , Qin Kai , Zheng Zhou-San , Chen Cui , Weng Hui-Wen , Yun Miao , Ye Sheng , Xu Rui-Hua , Xie Dan
Published: April 2019

Background

Metastasis remains the main cause of cancer-related death for gastric cancer (GC) patients, but the mechanisms are poorly understood. Using The Cancer Genome Atlas (TCGA) data base and bioinformatics analyses, we identified C12orf59 might act as a potential oncogenic protein in GC.

Methods

We investigate the expression pattern and clinical significance of C12orf59 in two independent cohorts of GC samples. In the training cohort, we used the X-tile program software to generate the optimal cutoff value for C12orf59 expression in order to classify patients accurately according to clinical outcome. In the validation cohort, this derived cutoff score was applied to exam the association of C12orf59 expression with survival outcome. A series of in vivo and in vitro assays were then performed to investigate the function of C12orf59 in GC.

Results

C12orf59 was significantly upregulated, and associated with poor survival outcome in two cohorts of GC samples. Gain- and loss of- function studies demonstrated C12orf59 promotes GC cell invasive and metastatic capacity both in vitro and in vivo, and induces epithelial–mesenchymal transition and angiogenesis. Mechanically, C12orf59 exerts oncogenic functions by up-regulating CDH11 expression via NF-κB signaling. Interesting, CDH11 could in turn promote NF-κB bind to C12orf59’s promoter and form a positive feedback loop to sustain the metastatic ability of GC cells. Additionally, downregulation of miR-654-5p is another important mechanism for C12orf59 overexpression in GC.

Conclusion

Our finding suggested the newly identified C12orf59/NF-κB/CDH11 feedback loop may represent a new strategy for GC treatment.
The trials and tribulations of conducting an m-health pilot randomized controlled trial to improve oral cancer therapy adherence: recommendations for future multisite, non-drug clinical trials
Authors: Russell Lahiru , Pascoe Michaela C. , Seymour John F. , Aranda Sanchia , Butow Phyllis , Gough Karla , Schofield Penelope
Published: April 2019

Objective

Integrating mobile phone-based health (m-health) interventions into healthcare systems is one solution to improve access to services for the growing number of patients with chronic illness. Practical challenges such as poor recruitment and inadequate resource allocation can hamper the assessment of such interventions with clinical trial methodology. This paper highlights the challenges encountered during a pilot randomized controlled trial of an m-health medication adherence intervention and offers recommendations for future multi-site, non-drug clinical trials.

Results

Eighteen patients were recruited to the study; eight were randomly allocated to the intervention arm. Intervention participants responded to their daily medication-reminder text messages, indicating that medication had been taken or not, and nurses were able to organize their calls around their workload. The trial closed prematurely primarily due to inadequate numbers of eligible patients; however, other potentially resolvable feasibility issues were identified. These included lack of infrastructure at study sites, poor screening data acquisition and management processes, and inexperience in conducting supportive care trials at participating sites. M-health intervention trials are designed to inform implementation of best supportive care practice. Adequate skills and infrastructure are research prerequisites that require careful consideration and sufficient investment for the successful execution of multi-site supportive care trials.

Trial registration Australian and New Zealand Clinical Trials Register: ACTRN12612000635864
Effects of restrictions on maternal feed intake on the immune indexes of umbilical cord blood and liver Toll-like receptor signaling pathways in fetal goats during pregnancy
Authors: Chen Wenxun , Yan Qiongxian , Yang Hong , Zhou Xiaoling , Tan Zhiliang
Published: April 2019

Background

Liver has important immune function during fetal development and after birth. However, the effect of maternal malnutrition on immune function of the fetal liver is rarely reported. In this study, twelve pregnant goats (Xiangdong black goat, at d 45 of gestation) were assigned to the control group (fed 100% of nutritional requirements) and the restriction group (fed 60% of the intake of the control group) during gestation from d 55 to 100. Fetal goats were harvested at d 100 of gestation and immune indexes and amino acid profiles of the umbilical cord blood and liver Toll-like receptors (TLRs) signaling pathways were measured.

Results

Maternal body weight in the restriction group was lower than the control group (P < 0.05). Maternal feed intake restriction decreased (P < 0.05) heart weight, heart index, alkaline phosphatase and serum amyloid protein A in the umbilical cord blood (UCB). Moreover, only histidine was decreased in the restricted group (P = 0.084), and there were no differences in other amino acids contents in the UCB between the two groups (P > 0.05). The TLR2 and TLR4 mRNA expression in the fetal liver in the restriction group was greater (P < 0.05) than that in the control group. Furthermore, the mRNA expression levels of myeloid differentiation primary response 88 (MyD88), TNF receptor associated factor 6, nuclear factor kappa B subunit 1, NFKB inhibitor alpha, IFN-β, TGF-β, TNF-α and IL-1β in the restricted group were upregulated (P < 0.05), and the expression of TLR3 (P = 0.099) tended to be higher in the restricted group. However, protein levels of TLR2, TLR4, IκBα, phosphorylated IκBα, phosphorylated IκBα/total IκBα, TRIF and MyD88 were not affected (P > 0.05) by maternal intake restriction.

Conclusions

These results revealed that the restriction of maternal feed intake influenced the development of heart and hepatic protein synthesis at the acute phase of fetal goats and upregulated the mRNA expression of genes involved in MyD88-dependent signaling pathways and of target cytokines.
Sex Differences in Effects of Obesity on Reproductive Hormones and Glucose Metabolism in Early Puberty
Authors: Nokoff Natalie , Thurston Jessica , Hilkin Allison , Pyle Laura , Zeitler Philip S , Nadeau Kristen J , Santoro Nanette , Kelsey Megan M
Published: April 2019

Context

Obesity is known to impact reproductive function in adults, but little is known about its effects on reproductive hormones during puberty.

Objective

To assess sex differences in effects of obesity on reproductive hormones and their relation to insulin sensitivity and secretion.

Design

Cross-sectional study including anthropometrics, serum and urine reproductive hormone concentrations, and intravenous glucose tolerance testing (IVGTT) to assess acute insulin response to glucose (AIRg), and insulin sensitivity (Si).

Setting

Outpatient academic clinical research center.

Patients

Girls (52%) and boys (48%) who were normal weight (NW; n = 51, BMI-Z score = −0.11 ± 0.77, age = 11.5 ± 1.7 years) and obese (n = 53, BMI-Z score = 2.22 ± 0.33, age = 10.9 ± 1.5 years), Tanner stage 2 to 3.

Results

Boys with obesity had lower total testosterone (P < 0.0001) and higher concentrations of the urinary estradiol metabolite, E1c, (P = 0.046) than boys with NW. Girls with obesity had higher free androgen index (FAI; P = 0.03) than NW girls. Both boys and girls with obesity had lower sex hormone-binding globulin (SHBG; P < 0.0001) than NW. AIRg was inversely related to SHBG in boys (R = 0.6, P < 0.0001) and girls (R = 0.53, P = 0.0001). Si correlated with higher SHBG in boys (R2 = 0.67, P < 0.0001) and girls (R = 0.5, P = 0.0003), higher total testosterone for boys (R = 0.39, P = 0.01), and lower FAI for girls (R = −0.2, P = 0.04).

Conclusion

Youth with obesity have lower SHBG than youth with NW, but obesity has differential effects on reproductive hormones in girls versus boys, which are apparent early in puberty. Ongoing longitudinal studies will evaluate the impact of obesity on reproductive hormones in girls and boys as puberty progresses.
Exercise-Induced Mitophagy in Skeletal Muscle and Heart
Authors: Guan Yuntian , Drake Joshua C. , Yan Zhen
Published: April 2019

Regular exercise enhances mitochondrial function by promoting healthy mitochondrial remodeling, but the underlying mechanisms are not thoroughly understood. An emerging hypothesis suggests that, in addition to anabolic events such as mitochondria biogenesis, the selective degradation of dysfunctional mitochondria (i.e., mitophagy) also is a key component of exercise-mediated adaptations in striated muscle, which eventually leads to better mitochondrial functions.
Preclinical neuroimaging of gene–environment interactions in psychiatric disease
Authors: Yi Sue Y. , Barnett Brian R. , Yu John-Paul J.
Published: April 2019

Psychiatric disease is one of the leading causes of disability worldwide. Despite the global burden and need for accurate diagnosis and treatment of mental illness, psychiatric diagnosis remains largely based on patient-reported symptoms, allowing for immense symptomatic heterogeneity within a single disease. In renewed efforts towards improved diagnostic specificity and subsequent evaluation of treatment response, a greater understanding of the underlying of the neuropathology and neurobiology of neuropsychiatric disease is needed. However, dissecting these mechanisms of neuropsychiatric illness in clinical populations are problematic with numerous experimental hurdles limiting hypothesis-driven studies including genetic confounds, variable life experiences, different environmental exposures, therapeutic histories, as well as the inability to investigate deeper molecular changes in vivo . Preclinical models, where many of these confounding factors can be controlled, can serve as a crucial experimental bridge for studying the neurobiological origins of mental illness. Furthermore, although behavioral studies and molecular studies are relatively common in these model systems, focused neuroimaging studies are very rare and represent an opportunity to link the molecular changes in psychiatric illness with advanced quantitative neuroimaging studies. In this review, we present an overview of well-validated genetic and environmental models of psychiatric illness, discuss gene–environment interactions, and examine the potential role of neuroimaging towards understanding genetic, environmental, and gene-environmental contributions to psychiatric illness.
Clinical trials in molecular radiotherapy—Tribulations and Triumphs Report of the NCRI CTRad meeting held at the Lift Islington, 8 June 2018
Authors: Falzone Nadia , Gregory Rebecca , Aldridge Matthew , Terry Samantha YA , Flux Glenn
Published: April 2019

It has been almost a decade since the commentary Molecular radiotherapy — the radionuclide raffle? by Gaze and Flux (2010). The overarching feeling then was that no individual or organisation has taken up the challenge, nationally or internationally, of championing molecular targeted radionuclide therapy in all its aspects. Here, we report on the recent NCRI–CTRad (Clinical Trials in Molecular Radiotherapy–Tribulations and Triumphs) meeting, held in London on the 8 June 2018. The meeting was organized by the NCRI–CTRad to review the challenges and opportunities for clinical trials in molecular radiotherapy, particularly focussing on investigator-led trials that incorporate imaging and dosimetry, and to discuss how the community can move forward. This meeting was organised in conjunction with the British Nuclear Medicine Society and reflects the progress of Nuclear Medicine in the UK.
Precision of aiming with a portable X-ray device (Nomad Pro 2) compared to a wall-mounted device in intraoral radiography
Authors: Hoogeveen Reinier C. , Meertens Bram R. , Berkhout W. Erwin R.
Published: April 2019

Background:

Hand-held (HH) X-ray devices are currently introduced for routine dentistry in some global areas. Safety issues are resolved but imaging quality aspects remain to be explored. Aim: To compare the aiming accuracy of two intraoral radiography devices: the portable Nomad Pro2 and the wall-mounted (WM) Planmeca Intra. Setting and design: In vitro experimentation involving radiologic mannequins and unbiased student operators.

Methods and materials:

20 operators obtained intraoral radiographs of four regions (bitewing, upper molar, lower molar and upper anterior) in five mannequins, using HH and WM devices. Beam-aiming devices were fitted with metal cross-wires to project on image sensors. Deviation from ideal perpendicular incidence of beam was calculated, based on positions of cross-wires relative to gold-standard positions (i.e. average of 10-fold precise aiming by authors via WM system). Analytic models relied on Wilcoxon signed-rank test and mixed model analyses.

Results:

Mean deviations from perfect aim were 2.88˚ (± 1.80˚) for WM and 3.06˚ (± 1.90˚) for HH methods. The difference among all operators (HH vs WM) was 0.17˚ (± 2.48˚), which was not significant. Seven operators showed better aim by HH device (13 by WM system); and in one instance, this difference was significant.

Conclusions:

Aiming precision proved similar for HH and WM methods of intraoral radiography, although individual operators may perform better using one of these modalities. Aim is not an expected limiting factor for image quality in HH (vs WM) diagnostics.
Regulation of alternative splicing by p300-mediated acetylation of splicing factors
Authors: Siam Ahmad , Baker Mai , Amit Leah , Regev Gal , Rabner Alona , Najar Rauf Ahmad , Bentata Mercedes , Dahan Sara , Cohen Klil , Araten Sarah , Nevo Yuval , Kay Gillian , Mandel-Gutfreund Yael , Salton Maayan
Published: April 2019

Splicing of precursor mRNA (pre-mRNA) is an important regulatory step in gene expression. Recent evidence points to a regulatory role of chromatin-related proteins in alternative splicing regulation. Using an unbiased approach, we have identified the acetyltransferase p300 as a key chromatin-related regulator of alternative splicing. p300 promotes genome-wide exon inclusion in both a transcription-dependent and -independent manner. Using CD44 as a paradigm, we found that p300 regulates alternative splicing by modulating the binding of splicing factors to pre-mRNA. Using a tethering strategy, we found that binding of p300 to the CD44 promoter region promotes CD44v exon inclusion independently of RNAPII transcriptional elongation rate. Promoter-bound p300 regulates alternative splicing by acetylating splicing factors, leading to exclusion of hnRNP M from CD44 pre-mRNA and activation of Sam68. p300-mediated CD44 alternative splicing reduces cell motility and promotes epithelial features. Our findings reveal a chromatin-related mechanism of alternative splicing regulation and demonstrate its impact on cellular function.
Luminescent peptide tagging enables efficient screening for CRISPR-mediated knock-in in human induced pluripotent stem cells
Authors: Madsen Ralitsa R. , Semple Robert K.
Published: April 2019

Human pluripotent stem cells are increasingly used for CRISPR-mediated gene targeting in efforts to generate models of human diseases. This is a challenging task because of the high sensitivity of these cells to suboptimal conditions, including CRISPR-associated DNA damage and subsequent rounds of single-cell cloning. We sought to develop a sensitive method that enables rapid screening of CRISPR targeted cells, while preserving cell viability and eliminating the need for expensive sequencing of a large number of clones. A protocol was designed in which the luminescent peptide tag, HiBiT, is appended to the extracellular portion of an inert surface membrane protein (CD46), using synthetic CRISPR reagents and a widely distributed human induced pluripotent stem cell (iPSC) line. We find that this approach substantially reduces labour-intensive screening of CRISPR-targeted iPSCs and minimises the number of subcloning steps. Successfully edited iPSCs could be identified within a week of targeting, based only on extracellular luminescence detection in live cells. The total screening time in each round was less than 30 minutes and no sequencing was required. This method can be developed further to serve as a highly sensitive co-selection strategy in CRISPR knock-in experiments, particularly in the context of challenging cell lines.