bluuebunny/crossref_metadata_2025_split huggingface dataset:
Constitutively Expressed IFITM3 Protein in Human Endothelial Cells Poses an Early Infection Block to Human Influenza Viruses
Authors: Sun Xiangjie , Zeng Hui , Kumar Amrita , Belser Jessica A. , Maines Taronna R. , Tumpey Terrence M. 
Published: October 2016

ABSTRACT
A role for pulmonary endothelial cells in the orchestration of cytokine production and leukocyte recruitment during influenza virus infection, leading to severe lung damage, has been recently identified. As the mechanistic pathway for this ability is not fully known, we extended previous studies on influenza virus tropism in cultured human pulmonary endothelial cells. We found that a subset of avian influenza viruses, including potentially pandemic H5N1, H7N9, and H9N2 viruses, could infect human pulmonary endothelial cells (HULEC) with high efficiency compared to human H1N1 or H3N2 viruses. In HULEC, human influenza viruses were capable of binding to host cellular receptors, becoming internalized and initiating hemifusion but failing to uncoat the viral nucleocapsid and to replicate in host nuclei. Unlike numerous cell types, including epithelial cells, we found that pulmonary endothelial cells constitutively express a high level of the restriction protein IFITM3 in endosomal compartments. IFITM3 knockdown by small interfering RNA (siRNA) could partially rescue H1N1 virus infection in HULEC, suggesting IFITM3 proteins were involved in blocking human influenza virus infection in endothelial cells. In contrast, selected avian influenza viruses were able to escape IFITM3 restriction in endothelial cells, possibly by fusing in early endosomes at higher pH or by other, unknown mechanisms. Collectively, our study demonstrates that the human pulmonary endothelium possesses intrinsic immunity to human influenza viruses, in part due to the constitutive expression of IFITM3 proteins. Notably, certain avian influenza viruses have evolved to escape this restriction, possibly contributing to virus-induced pneumonia and severe lung disease in humans.

IMPORTANCE
Avian influenza viruses, including H5N1 and H7N9, have been associated with severe respiratory disease and fatal outcomes in humans. Although acute respiratory distress syndrome (ARDS) and progressive pulmonary endothelial damage are known to be present during severe human infections, the role of pulmonary endothelial cells in the pathogenesis of avian influenza virus infections is largely unknown. By comparing human seasonal influenza strains to avian influenza viruses, we provide greater insight into the interaction of influenza virus with human pulmonary endothelial cells. We show that human influenza virus infection is blocked during the early stages of virus entry, which is likely due to the relatively high expression of the host antiviral factors IFITMs (interferon-induced transmembrane proteins) located in membrane-bound compartments inside cells. Overall, this study provides a mechanism by which human endothelial cells limit replication of human influenza virus strains, whereas avian influenza viruses overcome these restriction factors in this cell type.
Effect of Transcutaneous Electrical Acupuncture Point Stimulation at Different Frequencies in a Rat Model of Neuropathic Pain
Authors: Yu Xiangdi , Zhang Fangxiang , Chen Bingning 
Published: October 2016

Background Acupuncture and related techniques are used worldwide to alleviate pain; however, their mechanisms of action are still not fully understood. In the present study, we investigated the effect of transcutaneous electrical acupuncture point stimulation (TEAS) at different frequencies in a chronic constriction injury (CCI) model of neuropathic pain in rats. Methods CCI was induced by ligating the common sciatic nerve, which produced neuropathic pain. 18 male Sprague–Dawley rats with CCI were randomly divided into three groups (n=6 each) that remained untreated (CCI group) or received TEAS at high frequency (CCI+TEAS-H group) or TEAS at low frequency (CCI+TEAS-L group). Rats in the CCI+TEAS-H group received high frequency stimulation (6–9 mA, 100 Hz) at GB34/GV26/ST36; those in the CCI+TEAS-L group received low frequency stimulation (6–9 mA, 2 Hz) at the same points. Rats in the control group had the same electrodes applied but received no stimulation. All three groups were subjected to behavioural studies after treatment. Expression of μ opioid receptors (MORs) in the L3–L5 dorsal root ganglion (DRG) was determined by immunofluorescence staining and Western blotting after treatment. Results Compared with the untreated CCI group, both mechanical allodynia and thermal hypergesia were significantly attenuated, and MOR expression in the DRG was significantly increased by low frequency TEAS treatment at GB34/GV26/ST36 (p<0.05). In contrast, no significant differences were observed between the CCI and CCI+TEAS-H groups. Conclusions The use of low frequency TEAS significantly mitigated neuropathic pain in this rat model, and its analgesic effect is likely mediated by upregulation of MOR expression in the DRG.
Strength Training for Adolescents with cerebral palsy (STAR): study protocol of a randomised controlled trial to determine the feasibility, acceptability and efficacy of resistance training for adolescents with cerebral palsy
Authors: Ryan Jennifer M , Theis Nicola , Kilbride Cherry , Baltzopoulos Vasilios , Waugh Charlie , Shortland Adam , Lavelle Grace , Noorkoiv Marika , Levin Wendy , Korff Thomas 
Published: October 2016

IntroductionGait is inefficient in children with cerebral palsy, particularly as they transition to adolescence. Gait inefficiency may be associated with declines in gross motor function and participation among adolescents with cerebral palsy. Resistance training may improve gait efficiency through a number of biomechanical and neural mechanisms. The aim of the Strength Training for Adolescents with cerebral palsy (STAR) trial is to evaluate the effect of resistance training on gait efficiency, activity and participation in adolescents with cerebral palsy. We also aim to determine the biomechanical and neural adaptations that occur following resistance training and evaluate the feasibility and acceptability of such an intervention for adolescents with cerebral palsy.Methods and analysis60 adolescents (Gross Motor Function Classification System level I–III) will be randomised to a 10-week resistance training group or a usual care control group according to a computer-generated random schedule. The primary outcome is gait efficiency. Secondary outcomes are habitual physical activity, participation, muscle–tendon mechanics and gross motor function. General linear models will be used to evaluate differences in continuous data between the resistance training and usual care groups at 10 and 22 weeks, respectively. A process evaluation will be conducted alongside the intervention. Fidelity of the resistance training programme to trial protocol will be quantified by observations of exercise sessions. Semistructured interviews will be conducted with participants and physiotherapists following the resistance training programme to determine feasibility and acceptability of the programme.Ethics and disseminationThis trial has ethical approval from Brunel University London's Department of Clinical Sciences' Research Ethics Committee and the National Research Ethics Service (NRES) Committee London—Surrey Borders. The results of the trial will be submitted for publication in academic journals, presented at conferences and distributed to adolescents, families and healthcare professionals through the media with the assistance of the STAR advisory group.Trial registration numberISRCTN90378161; Pre-results.
A work observation study of nuclear medicine technologists: interruptions, resilience and implications for patient safety
Authors: Larcos George , Prgomet Mirela , Georgiou Andrew , Westbrook Johanna 
Published: October 2016

BackgroundErrors by nuclear medicine technologists during the preparation of radiopharmaceuticals or at other times can cause patient harm and may reflect the impact of interruptions, busy work environments and deficient systems or processes. We aimed to: (a) characterise the rate and nature of interruptions technologists experience and (b) identify strategies that support safety.MethodsWe performed 100 hours of observation of 11 technologists at a major public hospital and measured the proportions of time spent in eight categories of work tasks, location of task, interruption rate and type and multitasking (tasks conducted in parallel). We catalogued specific safety-oriented strategies used by technologists.ResultsTechnologists completed 5227 tasks and experienced 569 interruptions (mean, 4.5 times per hour; 95% CI 4.1 to 4.9). The highest interruption rate occurred when technologists were in transit between rooms (10.3 per hour (95% CI 8.3 to 12.5)). Interruptions during radiopharmaceutical preparation occurred a mean of 4.4 times per hour (95% CI 3.3 to 5.6). Most (n=426) tasks were interrupted once only and all tasks were resumed after interruption. Multitasking occurred 16.6% of the time. At least some interruptions were initiated by other technologists to convey important information and/or to render assistance. Technologists employed a variety of verbal and non-verbal strategies in all work areas (notably in the hot-lab) to minimise the impact of interruptions and optimise the safe conduct of procedures. Although most were due to individual choices, some strategies reflected overt or subliminal departmental policy.ConclusionsSome interruptions appear beneficial. Technologists' self-initiated strategies to support safe work practices appear to be an important element in supporting a resilient work environment in nuclear medicine.
Image-based teleconsultation using smartphones or tablets: qualitative assessment of medical experts
Authors: Boissin Constance , Blom Lisa , Wallis Lee , Laflamme Lucie 
Published: October 2016

BackgroundMobile health has promising potential in improving healthcare delivery by facilitating access to expert advice. Enabling experts to review images on their smartphone or tablet may save valuable time. This study aims at assessing whether images viewed by medical specialists on handheld devices such as smartphones and tablets are perceived to be of comparable quality as when viewed on a computer screen.MethodsThis was a prospective study comparing the perceived quality of 18 images on three different display devices (smartphone, tablet and computer) by 27 participants (4 burn surgeons and 23 emergency medicine specialists). The images, presented in random order, covered clinical (dermatological conditions, burns, ECGs and X-rays) and non-clinical subjects and their perceived quality was assessed using a 7-point Likert scale. Differences in devices' quality ratings were analysed using linear regression models for clustered data adjusting for image type and participants’ characteristics (age, gender and medical specialty).ResultsOverall, the images were rated good or very good in most instances and more so for the smartphone (83.1%, mean score 5.7) and tablet (78.2%, mean 5.5) than for a standard computer (70.6%, mean 5.2). Both handheld devices had significantly higher ratings than the computer screen, even after controlling for image type and participants' characteristics. Nearly all experts expressed that they would be comfortable using smartphones (n=25) or tablets (n=26) for image-based teleconsultation.ConclusionThis study suggests that handheld devices could be a substitute for computer screens for teleconsultation by physicians working in emergency settings.
Leadership and the medical registrar: how can organisations support these unsung heroes?
Authors: Blake Tim , Whallett Andrew 
Published: October 2016

Abstract
Medical registrars have been described as the ‘workhorses’ of National Health Service hospitals, being at the interface of acute and chronic health services. They are expected to demonstrate effective leadership skills. There are concerns from the Royal College of Physicians that medical registrars are being overwhelmed and unsupported by organisations, and are struggling in their ability to provide safe, high-quality patient care. Junior colleagues are also being deterred by general medical specialties by the prospect of becoming the ‘Med Reg’. There is a growing need to support medical registrars in several key aspects of training, not least medical leadership. Thus far, there has been a distinct disparity in the provision of medical leadership training for junior doctors in the UK that has adversely affected the standard of care given to patients. Recent landmark reviews and initiatives, principally the Medical Leadership Competency Framework, have raised awareness of leadership competencies for all doctors and the need for their incorporation into undergraduate and postgraduate curricula. It is hoped that interactive strategies to engage medical registrars in leadership training will lead to positive results including improvements in interdisciplinary communication, patient outcomes and fulfilment of curriculum competencies. Organisations have a duty to improve the quality of medical leadership training so that doctors feel equipped to influence change throughout their careers and be tomorrow's leaders. This review outlines the deficiencies in training, the importance of developing leadership skills in medical registrars and educational strategies that could be implemented by organisations in a cost-effective manner.
An evidence-based review of recent advances in therapy for heart failure with reduced ejection fraction (HFrEF)
Authors: Raj Leah , Adhyaru Bhavin 
Published: October 2016

Abstract
An estimated 5.1 million Americans have chronic heart failure and this is expected to increase 25% by 2030. Heart failure is a clinical syndrome that evolves from either functional or structural changes to the ventricles that lead to filling or ejection abnormalities. Thus far, pharmacotherapy has been show to be beneficial in patients only with reduced ejection fraction; however, new therapies have been developed in hopes of reducing the burden of heart failure. In this review, we will discuss current pharmacotherapies recommended in American College of Cardiology/American Heart Association guidelines, the evidence behind these recommendations as well as new and emerging therapies that have been developed.
Differences and similarities between emplacement models of kimberlite and basaltic maar-diatreme volcanoes
Authors: Kurszlaukis Stephan , Lorenz Volker 
Published: October 2016

Abstract
Most kimberlite maar-diatreme volcanoes erupted during the Tertiary or earlier and therefore their tephra rings and, less often, their near-surface diatreme-filling deposits have usually been eliminated by erosion. Poorly eroded Quaternary non-kimberlite maar-diatreme volcanoes, especially those of mafic and ultramafic magma types, have the same diatreme size range (diameter and depth) as kimberlite pipes and show similar internal volcaniclastic diatreme lithofacies. In addition, these young volcanoes often have a more or less preserved tephra ring consisting of hundreds to perhaps a few thousand thin tephra beds. Volcanological analyses of the xenolith-rich primary volcaniclastic deposits both within these diatremes and in the tephra ring beds reflect phases of explosive pipe growth and are of convincingly phreatomagmatic origin.
The similarities between non-kimberlite pipes and kimberlite pipes suggest to some researchers that phreatomagmatic processes were also responsible for pipe excavation processes in kimberlite maar-diatreme volcanoes. In contrast, other researchers have suggested that kimberlite maar-diatreme volcanoes were emplaced largely by magmatic processes as a consequence of exsolution and the explosive expansion of juvenile volatiles. We therefore analysed and compared some key geological features of kimberlite and ultrabasic to basic ‘basaltic’ maar-diatreme volcanoes to determine similarities and differences with respect to their emplacement behaviour.
Small-Molecule Disruption of the Myb/p300 Cooperation Targets Acute Myeloid Leukemia Cells
Authors: Uttarkar Sagar , Piontek Therese , Dukare Sandeep , Schomburg Caroline , Schlenke Peter , Berdel Wolfgang E. , Müller-Tidow Carsten , Schmidt Thomas J. , Klempnauer Karl-Heinz 
Published: October 2016

Abstract
The transcription factor c-Myb is essential for the proliferation of hematopoietic cells and has been implicated in the development of leukemia and other human cancers. Pharmacologic inhibition of Myb is therefore emerging as a potential therapeutic strategy for these diseases. By using a Myb reporter cell line, we have identified plumbagin and several naphthoquinones as potent low-molecular weight Myb inhibitors. We demonstrate that these compounds inhibit c-Myb by binding to the c-Myb transactivation domain and disrupting the cooperation of c-Myb with the coactivator p300, a major driver of Myb activity. Naphthoquinone-induced inhibition of c-Myb suppresses Myb target gene expression and induces the differentiation of the myeloid leukemia cell line HL60. We demonstrate that murine and human primary acute myeloid leukemia cells are more sensitive to naphthoquinone-induced inhibition of clonogenic proliferation than normal hematopoietic progenitor cells. Overall, our work demonstrates for the first time the potential of naphthoquinones as small-molecule Myb inhibitors that may have therapeutic potential for the treatment of leukemia and other tumors driven by deregulated Myb. Mol Cancer Ther; 15(12); 2905–15. ©2016 AACR.
Stress Effects in Vowel Perception as a Function of Language-Specific Vocabulary Patterns
Authors: Warner Natasha , Cutler Anne 
Published: October 2016

Abstract
Background/Aims: Evidence from spoken word recognition suggests that for English listeners, distinguishing full versus reduced vowels is important, but discerning stress differences involving the same full vowel (as in mu- from music or museum) is not. In Dutch, in contrast, the latter distinction is important. This difference arises from the relative frequency of unstressed full vowels in the two vocabularies. The goal of this paper is to determine how this difference in the lexicon influences the perception of stressed versus unstressed vowels. Methods: All possible sequences of two segments (diphones) in Dutch and in English were presented to native listeners in gated fragments. We recorded identification performance over time throughout the speech signal. The data were here analysed specifically for patterns in perception of stressed versus unstressed vowels. Results: The data reveal significantly larger stress effects (whereby unstressed vowels are harder to identify than stressed vowels) in English than in Dutch. Both language-specific and shared patterns appear regarding which vowels show stress effects. Conclusion: We explain the larger stress effect in English as reflecting the processing demands caused by the difference in use of unstressed vowels in the lexicon. The larger stress effect in English is due to relative inexperience with processing unstressed full vowels.
Epidemiology of first and recurrent venous thromboembolism in patients with active cancer
Authors: Katholing Anja , Rietbrock Stephan , Bamber Luke , Martinez Carlos , Cohen Alexander T. 
Published: October 2016

SummaryPopulation studies on the incidence of venous thromboembolism (VTE) in patients with active cancer are limited. An observational cohort study was undertaken to estimate the incidence of first and recurrent VTE. The source population consisted of all patients in the UK Clinical Practice Research Datalink, with additional information on hospitalisation and cause of death, between 2001 and 2011. A cancer-related clinical diagnosis or therapy within the 90 days before or after a VTE constituted an active-cancer-associated VTE. Incidence rates of first VTE among patients with active cancer and incidence rates of recurrent VTE during the 10-year observational period after a first VTE event were estimated. Incidence rates of all-cause mortality and age- and gender-specific mortality were also calculated. There were 6,592 active-cancer-associated VTEs with a total of 112,738 cancer-associated person-years of observation. The incidence rate of first VTE in patients with active cancer was 5.8 (95 % confidence interval 5.7–6.0) per 100 person-years. A first VTE recurrence was observed in 591 patients. The overall incidence rate for recurrence was 9.6 (95 % confidence interval 8.8–10.4) per 100 person-years, with a peak at 22.1 in the first six months. Recurrence rates were similar after initial pulmonary embolism and after initial deep-vein thrombosis. The mortality risk after VTE was considerable, with 64.5 % mortality after one year and 88.1 % after 10 years. VTE in patients with active cancer is common and associated with high recurrence and mortality rates. Efforts are needed to prevent VTE and reduce recurrence, especially in the first year after VTE diagnosis.Supplementary Material to this article is available online at www.thrombosis-online.com.
Powerful Men and Boyhood Sexuality in K. Sello Duiker’s Thirteen Cents
Authors: Nabutanyi Edgar 
Published: October 2016

In Southern African postcolonial discourses, sexual violation is often deployed as an allegory for either patriarchal control or racial domination. This perhaps explains the huge archive of narratives of sexual violence in the Southern African literary canon. While this archive and its scholarship mainly concentrates on the experiences of women and girls, a substantial number of texts portraying the sexual abuse of boys from the region demand that scholarly attention is paid to this phenomenon. Does contemporary South African fiction’s privileging of the sexual violation of boys suggest that boys are as vulnerable to this form of violence in moments of national crisis as are girls and women? Reading K. Sello Duiker’s Thirteen Cents1 as a portrayal of the precarious intersection of post-apartheid familial dystopia on children’s bodies—articulated through under-age prostitution—I explore how fiction intervenes successfully to spotlight the susceptibility of boys to pederasty in moments of societal crisis. Additionally, I examine how homosexual prostitution is portrayed as a tool for survival for helpless boys, on the one hand, and exhibition of patriarchal power for the men that pay to have sex with these boys, on the other. I argue that the depiction of underage sex work of some boys in South African cities can help rescue these victims from being perceived as mere statistical footnotes to Southern African inequities and patriarchal power.