bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coaches’ Perspectives on Personal and Psychosocial Development in University Sport
Authors: Rathwell Scott , Young Bradley W. 
Published: January 2018

Evidence suggests Canadian university sport programs can foster positive development. Further, university coaches have claimed to focus on their athletes’ personal and psychosocial development. Despite coaches’ claims, little is known about university coaches’ strategies for enhancing positive development. The aim of the present study was to explore the role of the coach in fostering positive development in the university context from the perspective of coaches. Specifically, this study addressed two research questions: (a) Who was responsible for athletes’ development? and (b) What is the role of the coach in athletes’ development? Semi-structured open-ended interviews were conducted with 14 recommended Canadian university coaches (9 male and 5 female). Interviews were analyzed using an inductive approach. Coaches highlighted the conditions of university sport that foster positive development. In addition, the coaches described how they maximized athletes’ development by establishing a support network, building team culture, and empowering athletes.
The Madness of Microbiome: Attempting To Find Consensus “Best Practice” for 16S Microbiome Studies
Authors: Pollock Jolinda , Glendinning Laura , Wisedchanwet Trong , Watson Mick 
Published: January 2018

ABSTRACT
The development and continuous improvement of high-throughput sequencing platforms have stimulated interest in the study of complex microbial communities. Currently, the most popular sequencing approach to study microbial community composition and dynamics is targeted 16S rRNA gene metabarcoding. To prepare samples for sequencing, there are a variety of processing steps, each with the potential to introduce bias at the data analysis stage. In this short review, key information from the literature pertaining to each processing step is described, and consequently, general recommendations for future 16S rRNA gene metabarcoding experiments are made.
A Vaginal Tract Signal Detected by the Group B Streptococcus SaeRS System Elicits Transcriptomic Changes and Enhances Murine Colonization
Authors: Cook Laura C. C. , Hu Hong , Maienschein-Cline Mark , Federle Michael J. 
Published: January 2018

ABSTRACT

Streptococcus agalactiae
(group B streptococcus [GBS]) can colonize the human vaginal tract, leading to both superficial and serious infections in adults and neonates. To study bacterial colonization of the reproductive tract in a mammalian system, we employed a murine vaginal carriage model. Using transcriptome sequencing (RNA-Seq), the transcriptome of GBS growing
in vivo
during vaginal carriage was determined. Over one-quarter of the genes in GBS were found to be differentially regulated during
in vivo
colonization compared to laboratory cultures. A two-component system (TCS) homologous to the staphylococcal virulence regulator SaeRS was identified as being upregulated
in vivo
. One of the SaeRS targets,
pbsP
, a proposed GBS vaccine candidate, is shown to be important for colonization of the vaginal tract. A component of vaginal lavage fluid acts as a signal to turn on
pbsP
expression via SaeRS. These data demonstrate the ability to quantify RNA expression directly from the murine vaginal tract and identify novel genes involved in vaginal colonization by GBS. They also provide more information about the regulation of an important virulence and colonization factor of GBS,
pbsP
, by the TCS SaeRS.
Randomised controlled trial on the effect of internet-delivered computerised cognitive–behavioural therapy on patients with insomnia who remain symptomatic following hypnotics: a study protocol
Authors: Sato Daisuke , Yoshinaga Naoki , Nagai Eiichi , Hanaoka Hideki , Sato Yasunori , Shimizu Eiji 
Published: January 2018

IntroductionInsomnia has severe consequences for health. Primary care physicians in Japan commonly provide hypnotics, which is far from optimal. The recommended treatment for insomnia is cognitive–behavioural therapy (CBT). Access to trained therapists, however, is limited. Rather than face-to-face CBT, several researchers have studied internet-delivered computerised CBT (ICBT). This paper describes the study protocol for a randomised controlled trial (RCT) to evaluate effectiveness and feasibility of our newly developed five-step ICBT as an adjunct to usual care (UC) compared with UC alone for patients with insomnia who remain symptomatic following hypnotics.Methods and analysisThis proposed exploratory RCT comprises two parallel groups (ICBT+UC and UC alone) consisting of 15 participants each (n=30) diagnosed with insomnia who remain symptomatic after pharmacotherapy. We aim to evaluate the effectiveness of six intervention weeks. The primary outcome of insomnia severity will be the Pittsburgh Sleep Quality Index (PSQI) at week 6. Secondary outcomes include sleep onset latency, total sleep time, sleep efficiency extracted from PSQI, current feeling of refreshment and perceived soundness of sleep measured using visual analogue scale, number of awakenings, anxiety by Hospital Anxiety and Depression Scale, depression by Center for Epidemiologic Studies Depression Scale and quality of life by Euro Qol-5D. All measures will be assessed at weeks 0 (baseline), 6 (postintervention) and 12 (follow-up), and intention-to-treat analysis will be applied. The statistical analysis plan has been developed considering design of field materials.Ethics and disseminationThis study will be conducted at the academic outpatient clinic of Chiba University Hospital, Japan. Ethics approval was granted by the Institutional Review Board of Chiba University Hospital. All participants will be required to provide written informed consent. The trial will be implemented and reported in accordance with Consolidated Standards of Reporting Trials recommendations.Trial registration numberUMIN000021509; Pre-results.
Opportunities and barriers in paediatric pulse oximetry for pneumonia in low-resource clinical settings: a qualitative evaluation from Malawi and Bangladesh
Authors: King Carina , Boyd Nicholas , Walker Isabeau , Zadutsa Beatiwel , Baqui Abdullah H , Ahmed Salahuddin , Islam Mazharul , Kainja Esther , Nambiar Bejoy , Wilson Iain , McCollum Eric D 
Published: January 2018

ObjectiveTo gain an understanding of what challenges pulse oximetry for paediatric pneumonia management poses, how it has changed service provision and what would improve this device for use across paediatric clinical settings in low-income countries.DesignFocus group discussions (FGDs), with purposive sampling and thematic analysis using a framework approach.SettingCommunity, front-line outpatient, and hospital outpatient and inpatient settings in Malawi and Bangladesh, which provide paediatric pneumonia care.ParticipantsHealthcare providers (HCPs) from Malawi and Bangladesh who had received training in pulse oximetry and had been using oximeters in routine paediatric care, including community healthcare workers, non-physician clinicians or medical assistants, and hospital-based nurses and doctors.ResultsWe conducted six FGDs, with 23 participants from Bangladesh and 26 from Malawi. We identified five emergent themes: trust, value, user-related experience, sustainability and design. HCPs discussed the confidence gained through the use of oximeters, resulting in improved trust from caregivers and valuing the device, although there were conflicts between the weight given to clinical judgement versus oximeter results. HCPs reported the ease of using oximeters, but identified movement and physically smaller children as measurement challenges. Challenges in sustainability related to battery durability and replacement parts, however many HCPs had used the same device longer than 4 years, demonstrating robustness within these settings. Desirable features included back-up power banks and integrated respiratory rate and thermometer capability.ConclusionsPulse oximetry was generally deemed valuable by HCPs for use as a spot-check device in a range of paediatric low-income clinical settings. Areas highlighted as challenges by HCPs, and therefore opportunities for redesign, included battery charging and durability, probe fit and sensitivity in paediatric populations.Trial registration numberNCT02941237.
Are trends in billing for high-intensity emergency care explained by changes in services provided in the emergency department? An observational study among US Medicare beneficiaries
Authors: Burke Laura G , Wild Robert C , Orav E John , Hsia Renee Y 
Published: January 2018

ObjectiveThere has been concern that an increase in billing for high-intensity emergency care is due to changes in coding practices facilitated by electronic health records. We sought to characterise the trends in billing for high-intensity emergency care among Medicare beneficiaries and to examine the degree to which trends in high-intensity billing are explained by changes in patient characteristics and services provided in the emergency department (ED).Design, setting and participantsObservational study using traditional Medicare claims to identify ED visits at non-federal acute care hospitals for elderly beneficiaries in 2006, 2009 and 2012.Outcomes measuresBilling intensity was defined by emergency physician evaluation and management (E&M) codes. We tested for overall trends in high-intensity billing (E&M codes 99285, 99291 and 99292) and in services provided over time using linear regression models, adjusting for patient characteristics. Additionally, we tested for time trends in rates of admission to the hospital and to the intensive care unit (ICU). Next, we classified outpatient visits into 39 diagnosis categories and analysed the change in proportion of high-intensity visits versus the change in number of services. Finally, we quantified the extent to which trends in high-intensity billing are explained by changes in patient demographics and services provided in the ED using multivariable modelling.ResultsHigh-intensity visits grew from 45.8% of 671 103 visits in 2006 to 57.8% of 629 010 visits in 2012 (2.0% absolute increase per year; 95% CI 1.97% to 2.03%) as did the mean number of services provided for admitted (1.28 to 1.41; +0.02 increase in procedures per year; 95% CI 0.018 to 0.021) and discharged ED patients (7.1 to 8.6; +0.25 increase in services per year; 95% CI 0.245 to 0.255). There was a reduction in hospital admission rate from 40.1% to 35.9% (−0.68% per year; 95% CI −0.71% to −0.65%; P<0.001), while the ICU rate of admission rose from 11.7% to 12.3% (+0.11% per year; 95% CI 0.09% to 0.12%; P<0.001). When we stratified by diagnosis category, there was a moderate correlation between change in visits billed as high intensity and the change in mean number of services provided per visit (r=0.38; 95% CI 0.07 to 0.63). Trends in patient characteristics and services provided accounted moderately for the trend in practice intensity for outpatient visits (pseudo R2of 0.47) but very little for inpatient visits (0.051) and visits overall (0.148).ConclusionsIncreases in services provided in the ED moderately account for the trends in billing for high-intensity emergency care for outpatient visits.
Health science communication strategies used by researchers with the public in the digital and social media ecosystem: a systematic scoping review protocol
Authors: Fontaine Guillaume , Lavallée Andréane , Maheu-Cadotte Marc-André , Bouix-Picasso Julien , Bourbonnais Anne 
Published: January 2018

IntroductionThe optimisation of health science communication (HSC) between researchers and the public is crucial. In the last decade, the rise of the digital and social media ecosystem allowed for the disintermediation of HSC. Disintermediation refers to the public’s direct access to information from researchers about health science-related topics through the digital and social media ecosystem, a process that would otherwise require a human mediator, such as a journalist. Therefore, the primary aim of this scoping review is to describe the nature and the extent of the literature regarding HSC strategies involving disintermediation used by researchers with the public in the digital and social media ecosystem. The secondary aim is to describe the HSC strategies used by researchers, and the communication channels associated with these strategies.Methods and analysisWe will conduct a scoping review based on the Joanna Briggs Institute’s methodology and perform a systematic search of six bibliographical databases (CINAHL, EMBASE, IBSS, PubMed, Sociological Abstracts and Web of Science), four trial registries and relevant sources of grey literature. Relevant journals and reference lists of included records will be hand-searched. Data will be managed using the EndNote software and the Rayyan web application. Two review team members will perform independently the screening process as well as the full-text assessment of included records. Descriptive data will be synthesised in a tabular format. Data regarding the nature and the extent of the literature, the HSC strategies and the associated communication channels will be presented narratively.Ethics and disseminationThis review does not require institutional review board approval as we will use only collected and published data. Results will allow the mapping of the literature about HSC between researchers and the public in the digital and social media ecosystem, and will be published in a peer-reviewed journal.
Man in his 50s with chest pain and dyspnoea
Authors: Obayashi Yuki , Izumi Chisato , Nakagawa Yoshihisa 
Published: January 2018

Clinical introductionA man in his 50s with sudden-onset chest pain and dyspnoea was transferred to the emergency room. He had a history of aortic valve replacement due to aortic regurgitation with a mechanical valve 6 years previously. Heart rate was 90 bpm, and blood pressure was too low to measure. In the emergency room, he presented with severe dyspnoea and a chest X-ray showed severe lung congestion (figure 1A). ECG showed complete left bundle branch block. His respiratory status rapidly worsened, and he went into cardiopulmonary arrest. After cardiopulmonary resuscitation, transthoracic echocardiography was performed (figure 1B, online supplementary video 1).Supplementary file 1Figure 1(A) Chest X-ray. (B) Colour Doppler image from apical five-chamber view.QuestionWhat is the most likely cause of the patient’s cardiopulmonary arrest?Myocardial infarction in left main trunkAortic dissectionProsthetic valve thrombosisProsthetic valve embolisationPulmonary embolism
Sickness absence due to different musculoskeletal diagnoses by occupational class: a register-based study among 1.2 million Finnish employees
Authors: Pekkala Johanna , Rahkonen Ossi , Pietiläinen Olli , Lahelma Eero , Blomgren Jenni 
Published: January 2018

ObjectivesThose in lower occupational classes have an increased risk of sickness absence due to musculoskeletal diseases (MSDs), but studies examining the associations simultaneously across specified diagnostic groups within MSDs are lacking. We examined occupational class differences in the occurrence and length of long-term sickness absence due to different musculoskeletal diagnoses.MethodsA 70% random sample of employed Finns aged 25–64 years old at the end of 2013 was linked to data on sickness absence of over 10 working days obtained from The Social Insurance Institution of Finland and occupational class from Statistics Finland. Sickness absences due to MSDs initiated in 2014 were followed until the end of each episode for female (n=675 636) and male (n=604 715) upper non-manuals, lower non-manuals and manual workers. Negative binomial hurdle models were used to analyse the associations.ResultsWithin the studied MSDs, the most common causes of absence were back disorders, particularly back pain, and shoulder disorders. Osteoarthritis, disc disorders and rheumatoid arthritis induced the longest episodes of absence. Clear hierarchical class differences were found throughout, but the magnitude of the differences varied across the diagnostic causes. The largest class differences in the occurrence were detected in shoulder disorders and back pain. The class differences in length were greatest in rheumatoid arthritis, disc disorders and, among men, also in hip osteoarthritis.ConclusionsHierarchical occupational class differences were found across different MSDs, with large differences in back and shoulder disorders. Occupational class and diagnosis should be considered when attempting to reduce sickness absence due to MSDs.
Novel anti-tumour necrosis factor receptor-1 (TNFR1) domain antibody prevents pulmonary inflammation in experimental acute lung injury
Authors: Proudfoot Alastair , Bayliffe Andrew , O’Kane Cecilia M , Wright Tracey , Serone Adrian , Bareille Philippe Jean , Brown Vanessa , Hamid Umar I , Chen Younan , Wilson Robert , Cordy Joanna , Morley Peter , de Wildt Ruud , Elborn Stuart , Hind Matthew , Chilvers Edwin R , Griffiths Mark , Summers Charlotte , McAuley Daniel Francis 
Published: January 2018

BackgroundTumour necrosis factor alpha (TNF-α) is a pleiotropic cytokine with both injurious and protective functions, which are thought to diverge at the level of its two cell surface receptors, TNFR1 and TNFR2. In the setting of acute injury, selective inhibition of TNFR1 is predicted to attenuate the cell death and inflammation associated with TNF-α, while sparing or potentiating the protective effects of TNFR2 signalling. We developed a potent and selective antagonist of TNFR1 (GSK1995057) using a novel domain antibody (dAb) therapeutic and assessed its efficacy in vitro, in vivo and in a clinical trial involving healthy human subjects.MethodsWe investigated the in vitro effects of GSK1995057 on human pulmonary microvascular endothelial cells (HMVEC-L) and then assessed the effects of pretreatment with nebulised GSK1995057 in a non-human primate model of acute lung injury. We then tested translation to humans by investigating the effects of a single nebulised dose of GSK1995057 in healthy humans (n=37) in a randomised controlled clinical trial in which subjects were subsequently exposed to inhaled endotoxin.ResultsSelective inhibition of TNFR1 signalling potently inhibited cytokine and neutrophil adhesion molecule expression in activated HMVEC-L monolayers in vitro (P<0.01 and P<0.001, respectively), and also significantly attenuated inflammation and signs of lung injury in non-human primates (P<0.01 in all cases). In a randomised, placebo-controlled trial of nebulised GSK1995057 in 37 healthy humans challenged with a low dose of inhaled endotoxin, treatment with GSK1995057 attenuated pulmonary neutrophilia, inflammatory cytokine release (P<0.01 in all cases) and signs of endothelial injury (P<0.05) in bronchoalveolar lavage and serum samples.ConclusionThese data support the potential for pulmonary delivery of a selective TNFR1 dAb as a novel therapeutic approach for the prevention of acute respiratory distress syndrome.Trial registration numberClinicalTrials.gov NCT01587807.
Modulation of Macropinocytosis-Mediated Internalization Decreases Ocular Toxicity of Antibody–Drug Conjugates
Authors: Zhao Hui , Atkinson John , Gulesserian Sara , Zeng Zhilan , Nater Jenny , Ou Jimmy , Yang Peng , Morrison Karen , Coleman Jeffrey , Malik Faisal , Challita-Eid Pia , Karki Sher , Aviña Hector , Hubert René , Capo Linnette , Snyder Josh , Moon Sung-Ju , Luethy Roland , Mendelsohn Brian A. , Stover David R. , Doñate Fernando 
Published: January 2018

Abstract
AGS-16C3F is an antibody–drug conjugate (ADC) against ectonucleotide pyrophosphatase/phosphodiesterase 3 (ENPP3) containing the mcMMAF linker-payload currently in development for treatment of metastatic renal cell carcinoma. AGS-16C3F and other ADCs have been reported to cause ocular toxicity in patients by unknown mechanisms. To investigate this toxicity, we developed an in vitro assay using human corneal epithelial cells (HCEC) and show that HCECs internalized AGS-16C3F and other ADCs by macropinocytosis, causing inhibition of cell proliferation. We observed the same mechanism for target-independent internalization of AGS-16C3F in fibroblasts and human umbilical vein endothelial cells (HUVEC). Macropinocytosis-mediated intake of macromolecules is facilitated by the presence of positive charges or hydrophobic residues on the surface of the macromolecule. Modification of AGS-16C3F, either by attachment of poly-glutamate peptides, mutation of residue K16 to D on AGS-16C3F [AGS-16C3F(K16D)], or decreasing the overall hydrophobicity via attachment of polyethylene glycol moieties, significantly reduced cytotoxicity against HCECs and other primary cells. Rabbits treated with AGS-16C3F showed significant ocular toxicity, whereas those treated with AGS-16C3F(K16D) presented with less severe and delayed toxicities. Both molecules displayed similar antitumor activity in a mouse xenograft model. These findings establish a mechanism of action for target-independent toxicities of AGS-16C3F and ADCs in general, and provide methods to ameliorate these toxicities.
Significance:These findings reveal a mechanism for nonreceptor-mediated toxicities of antibody drug conjugates and potential solutions to alleviate these toxicities. Cancer Res; 78(8); 2115–26. ©2018 AACR.
Mitotically-Associated lncRNA (MANCR) Affects Genomic Stability and Cell Division in Aggressive Breast Cancer
Authors: Tracy Kirsten M. , Tye Coralee E. , Ghule Prachi N. , Malaby Heidi L.H. , Stumpff Jason , Stein Janet L. , Stein Gary S. , Lian Jane B. 
Published: January 2018

Abstract
Aggressive breast cancer is difficult to treat as it is unresponsive to many hormone-based therapies; therefore, it is imperative to identify novel, targetable regulators of progression. Long non-coding RNAs (lncRNA) are important regulators in breast cancer and have great potential as therapeutic targets; however, little is known about how the majority of lncRNAs function within breast cancer. This study characterizes a novel lncRNA, MANCR (mitotically-associated long noncoding RNA; LINC00704), which is upregulated in breast cancer patient specimens and cells. Depletion of MANCR in triple-negative breast cancer cells significantly decreases cell proliferation and viability, with concomitant increases in DNA damage. Transcriptome analysis, based on RNA sequencing, following MANCR knockdown reveals significant differences in the expression of &gt;2,000 transcripts, and gene set enrichment analysis identifies changes in multiple categories related to cell-cycle regulation. Furthermore, MANCR expression is highest in mitotic cells by both RT-qPCR and RNA in situ hybridization. Consistent with a role in cell-cycle regulation, MANCR-depleted cells have a lower mitotic index and higher incidences of defective cytokinesis and cell death. Taken together, these data reveal a role for the novel lncRNA, MANCR, in genomic stability of aggressive breast cancer, and identify it as a potential therapeutic target.
Implications: The novel lncRNA, MANCR (LINC00704), is upregulated in breast cancer and is functionally linked with cell proliferation, viability, and genomic stability. Mol Cancer Res; 16(4); 587–98. ©2018 AACR.