bluuebunny/crossref_metadata_2025_split huggingface dataset:
Knockout of Epstein-Barr Virus BPLF1 Retards B-Cell Transformation and Lymphoma Formation in Humanized Mice
Authors: Whitehurst Christopher B. , Li Guangming , Montgomery Stephanie A. , Montgomery Nathan D. , Su Lishan , Pagano Joseph S. 
Published: October 2015

ABSTRACT

BPLF1 of Epstein-Barr virus (EBV) is classified as a late lytic cycle protein but is also found in the viral tegument, suggesting its potential involvement at both initial and late stages of viral infection. BPLF1 possesses both deubiquitinating and deneddylating activity located in its N-terminal domain and is involved in processes that affect viral infectivity, viral DNA replication, DNA repair, and immune evasion. A recently constructed EBV BPLF1-knockout (KO) virus was used in conjunction with a humanized mouse model that can be infected with EBV, enabling the first characterization of BPLF1 function
in vivo
. Results demonstrate that the BPLF1-knockout virus is approximately 90% less infectious than wild-type (WT) virus. Transformation of human B cells, a hallmark of EBV infection, was delayed and reduced with BPLF1-knockout virus. Humanized mice infected with EBV BPLF1-knockout virus showed less weight loss and survived longer than mice infected with equivalent infectious units of WT virus. Additionally, splenic tumors formed in 100% of mice infected with WT EBV but in only 25% of mice infected with BPLF1-KO virus. Morphological features of spleens containing tumors were similar to those in EBV-induced posttransplant lymphoproliferative disease (PTLD) and were almost identical to cases seen in human diffuse large B-cell lymphoma. The presence of EBV genomes was detected in all mice that developed tumors. The results implicate BPLF1 in human B-cell transformation and tumor formation in humanized mice.

IMPORTANCE
Epstein-Barr virus infects approximately 90% of the world's population and is the causative agent of infectious mononucleosis. EBV also causes aggressive lymphomas in individuals with acquired and innate immune disorders and is strongly associated with diffuse large B-cell lymphomas, classical Hodgkin lymphoma, Burkitt lymphoma, and nasopharyngeal carcinoma (NPC). Typically, EBV initially infects epithelial cells in the oropharynx, followed by a lifelong persistent latent infection in B-cells, which may develop into lymphomas in immunocompromised individuals. This work is the first of its kind in evaluating the effects of EBV's BPLF1 in terms of pathogenesis and lymphomagenesis in humanized mice and implicates BPLF1 in B-cell transformation and tumor development. Currently, there is no efficacious treatment for EBV, and therapeutic targeting of BPLF1 may lead to a new path to treatment for immunocompromised individuals or transplant recipients infected with EBV.
Neuroanatomical Characteristics of Deep and Superficial Needling Using Li11 as An Example
Authors: Wu Meiling , Cui Jingjing , Xu Dongsheng , Zhang Kun , Jing Xianghong , Bai Wanzhu 
Published: October 2015

Objectives To compare the neuroanatomical characteristics of the deep and superficial tissues at acupuncture point LI11 using a neural tracing technique, in order to examine the neural basis of potential differences between deep and superficial needling techniques. Methods In order to mimic the situations of the deep and superficial needling, the retrograde neural tracer Alexa Fluor 488 conjugate of cholera toxin subunit B (AF488-CTB) was injected into the muscle or subcutaneous tissue, respectively, at acupuncture point LI11 in eight rats (n=4 each). Three days following injection, the distribution of motor and sensory neurons labelled with AF488-CTB was examined in the spinal cord and dorsal root ganglia (DRG) under a fluorescent microscope. Results For both types of injection, labelled motor and sensory neurons were distributed on the side ipsilateral to the injection in the spinal cord and DRG between spinal levels C5 and T1. The number of labelled motor neurons following intramuscular injection was significantly higher than subcutaneous injection. By contrast, the number of labelled sensory neurons following subcutaneous injection was significantly higher in number and extended over a greater number of spinal segments compared to intramuscular injection. Conclusions These data indicate that the motor and sensory innervation of muscle and subcutaneous tissue beneath LI11 differ, and suggest that acupuncture signals induced by deep and superficial needling stimulation may be transmitted through different neural pathways.
Optimising adherence to childhood pneumonia treatment: the design and development of patient instructions and a job aid for amoxicillin dispersible tablets
Authors: Ebels Kelly , Faulx Dunia , Gerth-Guyette Emily , Murunga Peninah , Mahapatro Samarendra , Das Manoja Kumar , Ginsburg Amy Sarah 
Published: October 2015

IntroductionPneumonia is the leading cause of death from infection in children worldwide. Despite global treatment recommendations that call for children with pneumonia to receive amoxicillin dispersible tablets, only one-third of children with pneumonia receive any antibiotics and many do not complete the full course of treatment. Poor adherence to antibiotics may be driven in part by a lack of user-friendly treatment instructions.ObjectiveIn order to optimise childhood pneumonia treatment adherence at the community level, we developed a user-friendly product presentation for caregivers and a job aid for healthcare providers (HCPs). This paper aims to document the development process and offers a model for future health communication tools.MethodsWe employed an iterative design process that included document review, key stakeholder interviews, engagement with a graphic designer and pre-testing design concepts among target users in India and Kenya. The consolidated criteria for reporting qualitative research were used in the description of results.ResultsThough resources for pneumonia treatment are available in some countries, their content is incomplete and inconsistent with global recommendations. Document review and stakeholder interviews provided the information necessary to convey to caregivers and recommendations for how to present this information. Target users in India and Kenya confirmed the need to support better treatment adherence, recommended specific modifications to design concepts and suggested the development of a companion job aid. There was a consensus among caregivers and HCPs that these tools would be helpful and improve adherence behaviours.ConclusionsThe development of user-friendly instructions for medications for use in low-resource settings is a critically important but time-intensive and resource-intensive process that should involve engagement with target audiences.
Developing and validating a risk prediction model for acute care based on frailty syndromes
Authors: Soong J , Poots A J , Scott S , Donald K , Bell D 
Published: October 2015

ObjectivesPopulation ageing may result in increased comorbidity, functional dependence and poor quality of life. Mechanisms and pathophysiology underlying frailty have not been fully elucidated, thus absolute consensus on an operational definition for frailty is lacking. Frailty scores in the acute medical care setting have poor predictive power for clinically relevant outcomes. We explore the utility of frailty syndromes (as recommended by national guidelines) as a risk prediction model for the elderly in the acute care setting.SettingEnglish Secondary Care emergency admissions to National Health Service (NHS) acute providers.ParticipantsThere were N=2 099 252 patients over 65 years with emergency admission to NHS acute providers from 01/01/2012 to 31/12/2012 included in the analysis.Primary and secondary outcome measuresOutcomes investigated include inpatient mortality, 30-day emergency readmission and institutionalisation. We used pseudorandom numbers to split patients into train (60%) and test (40%). Receiver operator characteristic (ROC) curves and ordering the patients by deciles of predicted risk was used to assess model performance. Using English Hospital Episode Statistics (HES) data, we built multivariable logistic regression models with independent variables based on frailty syndromes (10th revision International Statistical Classification of Diseases, Injuries and Causes of Death (ICD-10) coding), demographics and previous hospital utilisation. Patients included were those >65 years with emergency admission to acute provider in England (2012).ResultsFrailty syndrome models exhibited ROC scores of 0.624–0.659 for inpatient mortality, 0.63–0.654 for institutionalisation and 0.57–0.63 for 30-day emergency readmission.ConclusionsFrailty syndromes are a valid predictor of outcomes relevant to acute care. The models predictive power is in keeping with other scores in the literature, but is a simple, clinically relevant and potentially more acceptable measurement for use in the acute care setting. Predictive powers of the score are not sufficient for clinical use.
Does smoking cessation result in improved mental health? A comparison of regression modelling and propensity score matching
Authors: Taylor Gemma , Girling Alan , McNeill Ann , Aveyard Paul 
Published: October 2015

ObjectivesSmokers report that smoking is therapeutic; a recent meta-analysis suggests the contrary. However, the association in that review may be explained by group-membership bias and confounding. Propensity score matching (PSM) aims to produce causal estimates from observational data. We examined the association between cessation and change in mental health before and after PSM.DesignA secondary analysis of prospective data from 5 placebo-controlled randomised trials for smoking reduction.ParticipantsAll participants were adult smokers and had smoked for at least 3 years. Participants were excluded if they were pregnant, breast feeding, under psychiatric care, deemed to be unfit by a general practitioner or part of a cessation programme. In total, 937 participants provided smoking data at both 6-month and 12-month follow-ups. Of these, 68 were confirmed as abstinent at both 6 and 12 months and 589 as continuous smokers at both follow-ups.Primary outcomeChange in mental health (36-item Short Form Survey (SF-36), scored 0–100) from baseline (while all participants were smokers) to 12-month follow-up (after cessation) was compared between quitters and continuing smokers with and without adjustment, and after PSM.ResultsBefore matching, quitters’ mental health scores improved compared with continuing smokers’, the mean difference and 95% CI was 5.5 (1.6 to 9.4). After adjustment, the difference was 4.5 (0.6 to 8.5), and after PSM, the difference was 3.4 (−2.2 to 8.9).ConclusionsImprovements in mental health after smoking cessation may be partly but not completely explained by group membership bias and confounding.
Establishing the validity of English GP Patient Survey items evaluating out-of-hours care
Authors: Mounce Luke T A , Barry Heather E , Calitri Raffaele , Henley William E , Campbell John , Roland Martin , Richards Suzanne 
Published: October 2015

BackgroundA 2014 national audit used the English General Practice Patient Survey (GPPS) to compare service users’ experience of out-of-hours general practitioner (GP) services, yet there is no published evidence on the validity of these GPPS items.ObjectivesEstablish the construct and concurrent validity of GPPS items evaluating service users’ experience of GP out-of-hours care.MethodsCross-sectional postal survey of service users (n=1396) of six English out-of-hours providers. Participants reported on four GPPS items evaluating out-of-hours care (three items modified following cognitive interviews with service users), and 14 evaluative items from the Out-of-hours Patient Questionnaire (OPQ). Construct validity was assessed through correlations between any reliable (Cochran's α>0.7) scales, as suggested by a principal component analysis of the modified GPPS items, with the ‘entry access’ (four items) and ‘consultation satisfaction’ (10 items) OPQ subscales. Concurrent validity was determined by investigating whether each modified GPPS item was associated with thematically related items from the OPQ using linear regressions.ResultsThe modified GPPS item-set formed a single scale (α=0.77), which summarised the two-component structure of the OPQ moderately well; explaining 39.7% of variation in the ‘entry access’ scores (r=0.63) and 44.0% of variation in the ‘consultation satisfaction’ scores (r=0.66), demonstrating acceptable construct validity. Concurrent validity was verified as each modified GPPS item was highly associated with a distinct set of related items from the OPQ.ConclusionsMinor modifications are required for the English GPPS items evaluating out-of-hours care to improve comprehension by service users. A modified question set was demonstrated to comprise a valid measure of service users’ overall satisfaction with out-of-hours care received. This demonstrates the potential for the use of as few as four items in benchmarking providers and assisting services in identifying, implementing and assessing quality improvement initiatives.
Volume versus standard coils in the treatment of intracranial aneurysms
Authors: Kaesmacher Johannes , Müller-Leisse Christina , Huber Thomas , Boeckh-Behrens Tobias , Haller Bernhard , Shiban Ehab , Friedrich Benjamin , Zimmer Claus , Dorn Franziska , Prothmann Sascha 
Published: October 2015

BackgroundVolume coils were developed to improve occlusion rates of intracranial aneurysms. Previous studies have shown increased packing density and comparable occlusion rates, but subgroup analyses of aneurysm size have not been carried out.ObjectiveTo evaluate the safety and efficacy of the Penumbra Coil 400 (PC400) system in treating intracranial aneurysms compared with standard diameter coils.MethodsA monocentric retrospective case review of 260 aneurysms in 233 patients was carried out. In 37 aneurysms the PC400 system was used, while 223 aneurysms were treated with conventional coils. Previously treated aneurysms and aneurysms treated with flow diverters were excluded. Aneurysm and procedure characteristics, packing density, postprocedural and follow-up occlusion grades as well as coil compaction were evaluated.ResultsAneurysms treated with PC400 coils had higher volume (218.9 vs 47.1 mm3, p<0.001), wider necks (3.0 vs 2.5 mm, p=0.005), and greater dome/neck ratio (2.0 vs 1.6, p=0.001) in comparison with aneurysms treated with conventional coils. Compared with controls, in the PC400 group we achieved higher packing densities (43.2% vs 34.4%, p<0.001; in aneurysms ≥7 mm 42.2% vs 27.8%, p<0.001). On follow-up angiography we observed less coil compaction (23.8% vs 64.3%, p=0.003) and less aneurysm recurrence (14.3% vs 40.5%, p=0.046) in aneurysms ≥7 mm when using the PC400 system.ConclusionsUse of the PC400 system as opposed to conventional coils suggests that the PC400 system is safe and effective in treating intracranial aneurysms. Despite having been applied in a potentially more difficult-to-treat group, the use of PC400 was associated with less coil compaction and aneurysm recurrence in aneurysms ≥7 mm.
Pipeline embolization device for the treatment of vertebral artery aneurysms: the fate of covered branch vessels
Authors: Mazur Marcus D , Kilburg Craig , Wang Victor , Taussky Philipp 
Published: October 2015

IntroductionPreliminary studies suggest that flow-diverting stents may be suitable for the treatment of aneurysms of the posterior circulation. The safety and efficacy of using flow-diverting stents for vertebral artery (VA) aneurysms is not well defined.ObjectiveTo examine the fate of covering the posterior inferior cerebellar artery (PICA) in patients undergoing placement of a flow-diverting stent for VA aneurysm.MethodsConsecutive patients who underwent placement of a Pipeline Embolization Device (PED) for treatment of an aneurysm of the V4 segment of the VA between April 2012 and June 2015 at our institution were retrospectively evaluated. Angiograms were reviewed to determine the patency of the PICA when the vessel origin was covered by the PED.Results11 patients with VA aneurysms who underwent treatment with the PED were identified. In each case the device covered the origin of the PICA. Follow-up angiography in eight patients demonstrated thrombosis of the aneurysm with patency of the PICA.ConclusionsFlow-diverting stents can be used for the treatment of VA aneurysms. When appropriately sized to the vessel wall and positioned in the VA, the device may cover the origin of the PICA without impairing flow through the branching artery.
Efficacy and safety of long-acting β-agonist/long-acting muscarinic antagonist combinations in COPD: a network meta-analysis
Authors: Oba Yuji , Sarva Siva T , Dias Sofia 
Published: October 2015

BackgroundThe place of long-acting β agonist/long-acting muscarinic antagonist (LABA/LAMA) combinations in stable patients with COPD is not well defined. The purpose of this study was to systematically review the efficacy and safety of LABA/LAMA combinations.MethodsSeveral databases and manufacturers’ websites were searched for relevant clinical trials. Randomised control trials, at least 12 weeks duration, comparing a LABA/LAMA combination with placebo and/or monotherapy were included. The data were pooled using a network as well as a traditional direct comparison meta-analysis.ResultsTwenty-three trials with a total of 27 172 patients were included in the analysis. LABA/LAMA combinations were associated with a greater improvement in lung function, St. George's Respiratory Questionnaire (SGRQ) score, and Transitional Dyspnoea Index (TDI) than monotherapies. LABA/LAMA combinations were associated with a significantly greater proportion of SGRQ and TDI responders than monotherapies (OR 1.23 (95% credible interval (CrI) 1.06–1.39), OR 1.34 (95% CrI 1.19–1.50) versus LABAs and OR 1.24 (95% CrI 1.11–1.36), OR 1.31 (95% CrI 1.18–1.46) versus LAMAs, respectively) and fewer moderate-to-severe exacerbations compared with LABAs (HR 0.82 (95% CrI 0.73–0.93)), but not when compared with LAMAs (HR 0.92 (95% CrI 0.84–1.00)). There were no statistically significant differences associated with LABA/LAMA combinations compared with monotherapies in safety outcomes as well as in severe exacerbations.ConclusionsThe combination therapy was the most effective strategy in improving lung function, quality of life, symptom scores and moderate-to-severe exacerbation rates, and had similar effects on safety outcomes and severe exacerbations as compared with monotherapies.
Inhibition of Casein Kinase 1 Alpha Prevents Acquired Drug Resistance to Erlotinib in EGFR-Mutant Non–Small Cell Lung Cancer
Authors: Lantermann Alexandra B. , Chen Dongshu , McCutcheon Kaitlin , Hoffman Greg , Frias Elizabeth , Ruddy David , Rakiec Daniel , Korn Joshua , McAllister Gregory , Stegmeier Frank , Meyer Matthew J. , Sharma Sreenath V. 
Published: October 2015

Abstract
Patients with lung tumors harboring activating mutations in the EGF receptor (EGFR) show good initial treatment responses to the EGFR tyrosine kinase inhibitors (TKI) erlotinib or gefitinib. However, acquired resistance invariably develops. Applying a focused shRNA screening approach to identify genes whose knockdown can prevent and/or overcome acquired resistance to erlotinib in several EGFR-mutant non–small cell lung cancer (NSCLC) cell lines, we identified casein kinase 1 α (CSNK1A1, CK1α). We found that CK1α suppression inhibits the NF-κB prosurvival signaling pathway. Furthermore, downregulation of NF-κB signaling by approaches independent of CK1α knockdown can also attenuate acquired erlotinib resistance, supporting a role for activated NF-κB signaling in conferring acquired drug resistance. Importantly, CK1α suppression prevented erlotinib resistance in an HCC827 xenograft model in vivo. Our findings suggest that patients with EGFR-mutant NSCLC might benefit from a combination of EGFR TKIs and CK1α inhibition to prevent acquired drug resistance and to prolong disease-free survival. Cancer Res; 75(22); 4937–48. ©2015 AACR.
Potential Biases Introduced by Conflating Screening and Diagnostic Testing in Colorectal Cancer Screening Surveillance
Authors: Becker Elizabeth A. , Griffith Derek M. , West Brady T. , Janz Nancy K. , Resnicow Ken , Morris Arden M. 
Published: October 2015

Abstract
Background: Screening and postsymptomatic diagnostic testing are often conflated in cancer screening surveillance research. We examined the error in estimated colorectal cancer screening prevalence due to the conflation of screening and diagnostic testing.
Methods: Using data from the 2008 National Health Interview Survey, we compared weighted prevalence estimates of the use of all testing (screening and diagnostic) and screening in at-risk adults and calculated the overestimation of screening prevalence across sociodemographic groups.
Results: The population screening prevalence was overestimated by 23.3%, and the level of overestimation varied widely across sociodemographic groups (median, 22.6%; mean, 24.8%). The highest levels of overestimation were in non-Hispanic white females (27.4%), adults ages 50–54 years (32.0%), and those with the highest socioeconomic vulnerability [low educational attainment (31.3%), low poverty ratio (32.5%), no usual source of health care (54.4%), and not insured (51.6%); all P &lt; 0.001].
Conclusions: When the impetus for testing was not included, colorectal cancer screening prevalence was overestimated, and patterns of overestimation often aligned with social and economic vulnerability. These results are of concern to researchers who use survey data from the Behavioral Risk Factor Surveillance System (BRFSS) to assess cancer screening behaviors, as it is currently not designed to distinguish diagnostic testing from screening.
Impact: Surveillance research in cancer screening that does not consider the impetus for testing risks measurement error of screening prevalence, impeding progress toward improving population health. Ultimately, to craft relevant screening benchmarks and interventions, we must look beyond “what” and “when” and include “why.” Cancer Epidemiol Biomarkers Prev; 24(12); 1850–4. ©2015 AACR.